MRSA infection – Diagnosis and treatment

Diagnosis

Doctors diagnose MRSA by checking a tissue sample or nasal secretions for signs of drug-resistant bacteria. The sample is sent to a lab where it’s placed in a dish of nutrients that encourage bacterial growth.

But because it takes about 48 hours for the bacteria to grow, newer tests that can detect staph DNA in a matter of hours are now becoming more widely available.

Treatment

Both health care-associated and community-associated strains of MRSA still respond to certain antibiotics.

Doctors may need to perform emergency surgery to drain large boils (abscesses), in addition to giving antibiotics.

In some cases, antibiotics may not be necessary. For example, doctors may drain a small, shallow boil (abscess) caused by MRSA rather than treat the infection with drugs.

Preparing for your appointment

While you may initially consult your family doctor, he or she may refer you to a specialist, depending on which of your organs is affected by the infection. For example, he or she may refer you to a doctor trained in skin conditions (dermatologist) or a doctor trained in heart conditions (cardiologist).

What you can do

Before your appointment, you might want to write a list that includes:

• Detailed descriptions of your symptoms
• Information about medical problems you’ve had
• Information about the medical problems of your parents or siblings
• All the medications and dietary supplements you take
• Questions you want to ask the doctor

What to expect from your doctor

During your physical exam, your doctor will closely examine any skin cuts you may have. He or she might take a sample of tissue or liquid from the cuts for testing.

Dec. 01, 2020

Show references

1. Methicillin-resistant Staphylococcus aureus (MRSA). Centers for Disease Control and Prevention. https://www.cdc.gov/mrsa/community/index.html. Accessed Nov. 2, 2020.
2. Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Epidemiology. https://www.uptodate.com/contents/search. Accessed Nov. 2, 2020.
3. Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Treatment. https://www.uptodate.com/contents/search. Accessed Nov. 2, 2020.
4. AskMayoExpert. Methicillin-resistant Staphylococcus aureus (MRSA). Mayo Clinic; 2020.
5. Methicillin-resistant Staphylococcus infections (MRSA and MRSE). Elsevier Point of Care. Elsevier; 2020. https://www.clinicalkey.com. Accessed Nov. 2, 2020.
6. Ferri FF. Methicillin-resistant Staphylococcus aureus (MRSA). In: Ferri’s Clinical Advisor 2021. Elsevier; 2021. https://www.clinicalkey.com. Accessed Nov. 2, 2020.
7. Harris A. Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Prevention and control. https://www.uptodate.com/contents/search. Accessed Nov. 2, 2020.

Related

Products & Services

Show more products and services from Mayo Clinic

What It Is, Symptoms & Treatment

Overview

What is MRSA?

MRSA stands for Methicillin-resistant Staphylococcus aureus. It is a type of Staphylococcus aureus bacterium. These bacteria are resistant to common antibiotics, including methicillin. You may have read about MRSA being a superbug.

What is

Staphylococcus aureus (staph)?

Staphylococcus aureus (staph) bacteria live in the nose or on skin. You can harbor staph bacteria, including MRSA, and not know it. A healthcare expert might refer to this as bacterial colonization.

Colonized people (carriers) may one day develop an MRSA infection, or they might stay healthy.

Staph, including MRSA, bacteria live in these body parts:

• Armpits.
• Buttocks (your butt).
• Groin.
• Nose.

How common is MRSA?

Approximately 1 in 3 Americans are carriers of staph bacteria at any time. Up to half of these could be MRSA. It’s important to emphasize that Staph aureus or MRSA carriage is not a disease.

What are the types of MRSA infections?

Two categories of MRSA are:

• Hospital-associated (HA): HA-MRSA refers to MRSA infections that are associated with healthcare settings, such as hospitals and nursing homes.
• Community-associated (CA): CA-MRSA infections are those that occur in people who have not had a recent hospitalization or other contact with the healthcare system.

Who is at risk for MRSA infection?

MRSA infection affects all ages and genders. Animals can carry MRSA, although they often get it from people. Intravenous drug users who share needles are 16 times more likely to get MRSA infection.

Certain workers and members of the community are more at risk for MRSA infection. These include:

• Athletes.
• Healthcare professionals.
• Members of the military.
• Prison inmates.
• Students and employees at schools and child care centers.
• Veterinarians, farm workers and livestock workers.

Symptoms and Causes

What is the relationship between MRSA colonization and infection?

Many people who carry MRSA never get sick. The bacterium remains within the skin or mucosa where it has established colonization. Problems arise when MRSA on the skin surface in a colonized person enters the skin through a wound or other opening and invades deeper structures.

How does MRSA spread?

You can get colonized with MRSA through direct contact with an infected person or animal. MRSA can survive on surfaces for hours, sometimes weeks. You can pick up the bacteria by touching or sharing contaminated items, such as:

• Bedsheets.
• Clothes.
• Medical equipment.
• Sports equipment.
• Towels.
• Utensils.

What are the symptoms of MRSA infection?

MRSA can cause a skin rash or infection that looks like a spider bite or pimples. The red, swollen bumps may feel warm and be tender to touch. The rash may ooze.

MRSA can also cause deeper infections in different parts of the body. In severe infections the bacterium may invade the bloodstream, a situation which would be called a bloodstream infection. Symptoms of bloodstream infection include fever and chills.

Diagnosis and Tests

How is MRSA infection diagnosed?

To diagnose an MRSA infection, your healthcare provider will take a small sample of skin or discharge from an open wound. Your provider may order a blood test called a blood culture. A lab checks for MRSA in these samples.

Management and Treatment

What are different forms of MRSA infection?

MRSA infections can occur at various sites and may be serious, even life-threatening. Important MRSA infections include:

How is MRSA infection managed or treated?

The two principles of treating Staph aureus infections, including MRSA infections, are source control and antibiotic therapy:

• Source control: This refers to reducing the numbers of bacteria at the site of infection. In the case of skin infections, your provider may drain boils or abscesses. Other deeper infections may require more complicated surgery.
• Antibiotic treatment: The antibiotic used to treat the infection depends on whether the Staph aureus infection is or is not an MRSA infection.

What should I know about MRSA treatments?

Milder infections can be treated with oral antibiotics (antibiotic pills). More severe infections may require intravenous antibiotic treatment. It is very important to take all of the antibiotics exactly as your healthcare provider prescribes.

You should also call your provider if an infection doesn’t start to clear up within a few days of taking a prescribed antibiotic. You may need to go to the hospital for stronger intravenous antibiotics.

Prevention

How can I prevent MRSA infections?

You can lower your risk of getting MRSA by taking these steps:

• Keep wounds clean and bandaged.
• Don’t share personal items like towels and razors.
• Place a towel on a locker room bench before sitting on it naked.
• Regularly wash sheets, towels and workout clothes in the recommended water temperature. (Hot water isn’t necessary.) Dry everything in a dryer. You don’t need to use bleach or wash potentially contaminated items separately.
• Shower immediately after working out or participating in activities that increase your risk of MRSA exposure.
• Use disinfecting sprays that kill germs to wipe down high-touch areas like light switches, remote controls and athletic equipment. Check labels to find disinfectants that kill staph bacteria.
• Wash hands with hot water and soap for at least 20 seconds. Use alcohol-based hand sanitizer when hand-washing isn’t possible.

Outlook / Prognosis

What is the prognosis (outlook) for people who have a MRSA infection?

Most MRSA skin infections clear up with treatment. MRSA is most dangerous if it enters the bloodstream. MRSA bloodstream infections can be serious. A bloodstream infection requires immediate medical attention.

Living With

When should I call the doctor?

You should call your healthcare provider if you experience:

• Fever and chills.
• Infection that doesn’t improve after a few days of antibiotics.
• Rash.
• Signs of skin infection (abscesses or boils).

What questions should I ask my doctor?

You may want to ask your healthcare provider:

• What is the best treatment?
• What are treatment side effects?
• What should I do if I forget to take the medicine?
• What are signs of complications of the infection?

A note from Cleveland Clinic

Many people carry Staph aureus or MRSA bacteria in their skin or noses for varying periods of time and never know it. This is not a problem. In some people, MRSA bacteria cause painful skin infections or more serious invasive infections. People in hospitals or nursing homes are at increased risk for MRSA infections. But you can pick up the bacteria in community settings, too. Contact your healthcare provider if you develop a skin infection or show signs of MRSA.

What It Is, Symptoms & Treatment

Overview

What is MRSA?

MRSA stands for Methicillin-resistant Staphylococcus aureus. It is a type of Staphylococcus aureus bacterium. These bacteria are resistant to common antibiotics, including methicillin. You may have read about MRSA being a superbug.

What is

Staphylococcus aureus (staph)?

Staphylococcus aureus (staph) bacteria live in the nose or on skin. You can harbor staph bacteria, including MRSA, and not know it. A healthcare expert might refer to this as bacterial colonization.

Colonized people (carriers) may one day develop an MRSA infection, or they might stay healthy.

Staph, including MRSA, bacteria live in these body parts:

• Armpits.
• Buttocks (your butt).
• Groin.
• Nose.

How common is MRSA?

Approximately 1 in 3 Americans are carriers of staph bacteria at any time. Up to half of these could be MRSA. It’s important to emphasize that Staph aureus or MRSA carriage is not a disease.

What are the types of MRSA infections?

Two categories of MRSA are:

• Hospital-associated (HA): HA-MRSA refers to MRSA infections that are associated with healthcare settings, such as hospitals and nursing homes.
• Community-associated (CA): CA-MRSA infections are those that occur in people who have not had a recent hospitalization or other contact with the healthcare system.

Who is at risk for MRSA infection?

MRSA infection affects all ages and genders. Animals can carry MRSA, although they often get it from people. Intravenous drug users who share needles are 16 times more likely to get MRSA infection.

Certain workers and members of the community are more at risk for MRSA infection. These include:

• Athletes.
• Healthcare professionals.
• Members of the military.
• Prison inmates.
• Students and employees at schools and child care centers.
• Veterinarians, farm workers and livestock workers.

Symptoms and Causes

What is the relationship between MRSA colonization and infection?

Many people who carry MRSA never get sick. The bacterium remains within the skin or mucosa where it has established colonization. Problems arise when MRSA on the skin surface in a colonized person enters the skin through a wound or other opening and invades deeper structures.

How does MRSA spread?

You can get colonized with MRSA through direct contact with an infected person or animal. MRSA can survive on surfaces for hours, sometimes weeks. You can pick up the bacteria by touching or sharing contaminated items, such as:

• Bedsheets.
• Clothes.
• Medical equipment.
• Sports equipment.
• Towels.
• Utensils.

What are the symptoms of MRSA infection?

MRSA can cause a skin rash or infection that looks like a spider bite or pimples. The red, swollen bumps may feel warm and be tender to touch. The rash may ooze.

MRSA can also cause deeper infections in different parts of the body. In severe infections the bacterium may invade the bloodstream, a situation which would be called a bloodstream infection. Symptoms of bloodstream infection include fever and chills.

Diagnosis and Tests

How is MRSA infection diagnosed?

To diagnose an MRSA infection, your healthcare provider will take a small sample of skin or discharge from an open wound. Your provider may order a blood test called a blood culture. A lab checks for MRSA in these samples.

Management and Treatment

What are different forms of MRSA infection?

MRSA infections can occur at various sites and may be serious, even life-threatening. Important MRSA infections include:

How is MRSA infection managed or treated?

The two principles of treating Staph aureus infections, including MRSA infections, are source control and antibiotic therapy:

• Source control: This refers to reducing the numbers of bacteria at the site of infection. In the case of skin infections, your provider may drain boils or abscesses. Other deeper infections may require more complicated surgery.
• Antibiotic treatment: The antibiotic used to treat the infection depends on whether the Staph aureus infection is or is not an MRSA infection.

What should I know about MRSA treatments?

Milder infections can be treated with oral antibiotics (antibiotic pills). More severe infections may require intravenous antibiotic treatment. It is very important to take all of the antibiotics exactly as your healthcare provider prescribes.

You should also call your provider if an infection doesn’t start to clear up within a few days of taking a prescribed antibiotic. You may need to go to the hospital for stronger intravenous antibiotics.

Prevention

How can I prevent MRSA infections?

You can lower your risk of getting MRSA by taking these steps:

• Keep wounds clean and bandaged.
• Don’t share personal items like towels and razors.
• Place a towel on a locker room bench before sitting on it naked.
• Regularly wash sheets, towels and workout clothes in the recommended water temperature. (Hot water isn’t necessary.) Dry everything in a dryer. You don’t need to use bleach or wash potentially contaminated items separately.
• Shower immediately after working out or participating in activities that increase your risk of MRSA exposure.
• Use disinfecting sprays that kill germs to wipe down high-touch areas like light switches, remote controls and athletic equipment. Check labels to find disinfectants that kill staph bacteria.
• Wash hands with hot water and soap for at least 20 seconds. Use alcohol-based hand sanitizer when hand-washing isn’t possible.

Outlook / Prognosis

What is the prognosis (outlook) for people who have a MRSA infection?

Most MRSA skin infections clear up with treatment. MRSA is most dangerous if it enters the bloodstream. MRSA bloodstream infections can be serious. A bloodstream infection requires immediate medical attention.

Living With

When should I call the doctor?

You should call your healthcare provider if you experience:

• Fever and chills.
• Infection that doesn’t improve after a few days of antibiotics.
• Rash.
• Signs of skin infection (abscesses or boils).

What questions should I ask my doctor?

You may want to ask your healthcare provider:

• What is the best treatment?
• What are treatment side effects?
• What should I do if I forget to take the medicine?
• What are signs of complications of the infection?

A note from Cleveland Clinic

Many people carry Staph aureus or MRSA bacteria in their skin or noses for varying periods of time and never know it. This is not a problem. In some people, MRSA bacteria cause painful skin infections or more serious invasive infections. People in hospitals or nursing homes are at increased risk for MRSA infections. But you can pick up the bacteria in community settings, too. Contact your healthcare provider if you develop a skin infection or show signs of MRSA.

What It Is, Symptoms & Treatment

Overview

What is MRSA?

MRSA stands for Methicillin-resistant Staphylococcus aureus. It is a type of Staphylococcus aureus bacterium. These bacteria are resistant to common antibiotics, including methicillin. You may have read about MRSA being a superbug.

What is

Staphylococcus aureus (staph)?

Staphylococcus aureus (staph) bacteria live in the nose or on skin. You can harbor staph bacteria, including MRSA, and not know it. A healthcare expert might refer to this as bacterial colonization.

Colonized people (carriers) may one day develop an MRSA infection, or they might stay healthy.

Staph, including MRSA, bacteria live in these body parts:

• Armpits.
• Buttocks (your butt).
• Groin.
• Nose.

How common is MRSA?

Approximately 1 in 3 Americans are carriers of staph bacteria at any time. Up to half of these could be MRSA. It’s important to emphasize that Staph aureus or MRSA carriage is not a disease.

What are the types of MRSA infections?

Two categories of MRSA are:

• Hospital-associated (HA): HA-MRSA refers to MRSA infections that are associated with healthcare settings, such as hospitals and nursing homes.
• Community-associated (CA): CA-MRSA infections are those that occur in people who have not had a recent hospitalization or other contact with the healthcare system.

Who is at risk for MRSA infection?

MRSA infection affects all ages and genders. Animals can carry MRSA, although they often get it from people. Intravenous drug users who share needles are 16 times more likely to get MRSA infection.

Certain workers and members of the community are more at risk for MRSA infection. These include:

• Athletes.
• Healthcare professionals.
• Members of the military.
• Prison inmates.
• Students and employees at schools and child care centers.
• Veterinarians, farm workers and livestock workers.

Symptoms and Causes

What is the relationship between MRSA colonization and infection?

Many people who carry MRSA never get sick. The bacterium remains within the skin or mucosa where it has established colonization. Problems arise when MRSA on the skin surface in a colonized person enters the skin through a wound or other opening and invades deeper structures.

How does MRSA spread?

You can get colonized with MRSA through direct contact with an infected person or animal. MRSA can survive on surfaces for hours, sometimes weeks. You can pick up the bacteria by touching or sharing contaminated items, such as:

• Bedsheets.
• Clothes.
• Medical equipment.
• Sports equipment.
• Towels.
• Utensils.

What are the symptoms of MRSA infection?

MRSA can cause a skin rash or infection that looks like a spider bite or pimples. The red, swollen bumps may feel warm and be tender to touch. The rash may ooze.

MRSA can also cause deeper infections in different parts of the body. In severe infections the bacterium may invade the bloodstream, a situation which would be called a bloodstream infection. Symptoms of bloodstream infection include fever and chills.

Diagnosis and Tests

How is MRSA infection diagnosed?

To diagnose an MRSA infection, your healthcare provider will take a small sample of skin or discharge from an open wound. Your provider may order a blood test called a blood culture. A lab checks for MRSA in these samples.

Management and Treatment

What are different forms of MRSA infection?

MRSA infections can occur at various sites and may be serious, even life-threatening. Important MRSA infections include:

How is MRSA infection managed or treated?

The two principles of treating Staph aureus infections, including MRSA infections, are source control and antibiotic therapy:

• Source control: This refers to reducing the numbers of bacteria at the site of infection. In the case of skin infections, your provider may drain boils or abscesses. Other deeper infections may require more complicated surgery.
• Antibiotic treatment: The antibiotic used to treat the infection depends on whether the Staph aureus infection is or is not an MRSA infection.

What should I know about MRSA treatments?

Milder infections can be treated with oral antibiotics (antibiotic pills). More severe infections may require intravenous antibiotic treatment. It is very important to take all of the antibiotics exactly as your healthcare provider prescribes.

You should also call your provider if an infection doesn’t start to clear up within a few days of taking a prescribed antibiotic. You may need to go to the hospital for stronger intravenous antibiotics.

Prevention

How can I prevent MRSA infections?

You can lower your risk of getting MRSA by taking these steps:

• Keep wounds clean and bandaged.
• Don’t share personal items like towels and razors.
• Place a towel on a locker room bench before sitting on it naked.
• Regularly wash sheets, towels and workout clothes in the recommended water temperature. (Hot water isn’t necessary.) Dry everything in a dryer. You don’t need to use bleach or wash potentially contaminated items separately.
• Shower immediately after working out or participating in activities that increase your risk of MRSA exposure.
• Use disinfecting sprays that kill germs to wipe down high-touch areas like light switches, remote controls and athletic equipment. Check labels to find disinfectants that kill staph bacteria.
• Wash hands with hot water and soap for at least 20 seconds. Use alcohol-based hand sanitizer when hand-washing isn’t possible.

Outlook / Prognosis

What is the prognosis (outlook) for people who have a MRSA infection?

Most MRSA skin infections clear up with treatment. MRSA is most dangerous if it enters the bloodstream. MRSA bloodstream infections can be serious. A bloodstream infection requires immediate medical attention.

Living With

When should I call the doctor?

You should call your healthcare provider if you experience:

• Fever and chills.
• Infection that doesn’t improve after a few days of antibiotics.
• Rash.
• Signs of skin infection (abscesses or boils).

What questions should I ask my doctor?

You may want to ask your healthcare provider:

• What is the best treatment?
• What are treatment side effects?
• What should I do if I forget to take the medicine?
• What are signs of complications of the infection?

A note from Cleveland Clinic

Many people carry Staph aureus or MRSA bacteria in their skin or noses for varying periods of time and never know it. This is not a problem. In some people, MRSA bacteria cause painful skin infections or more serious invasive infections. People in hospitals or nursing homes are at increased risk for MRSA infections. But you can pick up the bacteria in community settings, too. Contact your healthcare provider if you develop a skin infection or show signs of MRSA.

Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

Infect Chemother. 2016 Dec; 48(4): 267–273.

¹ and ²

Eun Ju Choo

¹Division of Infectious Diseases, Department of Medicine, Soonchunhyang University Hospital, Bucheon, Korea.

Henry F. Chambers

²Division of Infectious Diseases, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA, USA.

¹Division of Infectious Diseases, Department of Medicine, Soonchunhyang University Hospital, Bucheon, Korea.

²Division of Infectious Diseases, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA, USA.

Corresponding author.Corresponding Author: Henry F. Chambers, MD. Division of Infectious Diseases, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA, USA. Tel: +1-415-206-5437, Fax: +1-415-648-8425, ude.fscu@srebmahC. yrneHCopyright © 2016 by The Korean Society of Infectious Diseases and Korean Society for ChemotherapyThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been cited by other articles in PMC.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of health care-associated infections. Vancomycin remains an acceptable treatment option. There has been a welcome increase in the number of agents available for the treatment of MRSA infection. These drugs have certain differentiating attributes and may offer some advantages over vancomycin, but they also have significant limitations. These agents provide some alternative when no other options are available.

Keywords: Methicillin-resistant Staphylcoccus aureus, Vancomycin, Treatment

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of serious nosocomial infections.

Vancomycin, a glycopeptide in clinical use for more than 50 years, still serves as the cornerstone of the treatment of drug-resistant Gram-positive infections. However, there are significant concerns owing to decreasing susceptibility to this agent among S. aureus. Furthermore, vancomycin is slowly bactericidal, which may be partly responsible for reported clinical failures in treatment of bacteremia and endocarditis. The growing awareness of the limitations of vancomycin has served as an impetus for development of newer agents. Emergence of non-susceptible MRSA strains and recognition of the frequent failure of vancomycin treatment of MRSA infection regardless of the minimum inhibitory concentration (MIC) of the isolate, provides evidence of the need for more effective therapies and therapeutic approaches.

Linezolid, daptomycin, telavancin and ceftaroline are drugs that have received regulatory approval in the last decade for the treatment of infections caused by drug-resistant Gram-positive pathogens. Although these drugs do have certain differentiating attributes and may offer some advantages over vancomycin, they also have significant limitations. More importantly, data from randomized clinical trials to support greater therapeutic efficacy of the newer agents compared with vancomycin in the treatment of serious MRSA infections are limited.

Vancomycin or daptomycin are the agents of choice for treatment of invasive MRSA infections [1]. Alternative agents that may be used for second-line or salvage therapy include telavancin, ceftaroline, and linezolid. Recent studies of treatment of MRSA bacteremia are reviewed.

Vancomycin

Vancomycin is the agent for which there is the greatest cumulative clinical experience for the treatment of MRSA bacteremia. Although vancomycin has been used for over 50 years, controversies still exist about best to use it. Outcomes may be improved when vancomycin is dosed to achieve to a pharmacokinetics/pharmacodynamics (PK/PD) target, which requires serum concentration monitoring, particularly in the setting of renal dysfunction. Although several studies have suggested that vancomycin MIC = 2 μg/mL is associated with an increased risk of failure of treatment of these infections, a recent meta-analysis did not support this conclusion [2].

The pharmacokinetic driver of efficacy of vancomycin in bacteremia due to S. aureus is area under the plasma concentration time curve (AUC) values and an AUC_0-24h to MIC ratio of ≥400μg·h/mL has been suggested as the target value. The measured trough concentration of 15-20 mg/L alone as been used as a surrogate as it was thought to be predictive of AUC/MIC; recent evidence suggests this may be incorrect. Modeling studies have demonstrated that unadjusted extrapolation of AUC from serum trough concentrations underestimate AUC by up to 25% and that AUCs varied between patients with similar trough results by up to 30-fold [3]. The increased accuracy of AUC estimations from serum vancomycin concentrations by the addition of Bayesian analysis may allow more precise individualized dosing, especially for targeting treatment of infections due to MRSA with an MIC = 2 μg/mL.

The use of loading dose and ongoing weight-based dosing are critical to rapid achievement of adequate serum concentrations, the importance of which has been demonstrated by the finding in patients with MRSA-associated septic shock that the highest survival rates were associated with an AUC_0-24h/MIC well in excess of 400 [4]. Individualized dosing should be explored in selected patients populations like the critically ill or in intensive care.

In general, if there is a poor clinical response to vancomycin regardless of MIC, but especially if vancomycin MIC approaches the upper limit of the susceptible ranges (2 μg/mL), it should discontinued and therapy switched to an alternative agent, typically daptomycin.

Teicoplanin

Teicoplanin is a glycopeptides with slow bactericidal activity and a spectrum of activity and efficacy camparable to vancomycin. Some use it as the drug of choice for initial therapy of MRSA bacteremia, although good evidence to support this practice is lacking, while others favor its use for patients with intolerance to vancomycin [5]. Much debate has surrounded this antibiotic, however due to data showing inferior efficacy compared with vancomycin. These results can be explained by inadequate dosing of teicoplanin secondary to greater protein binding compared with vancomycin. Recent data and meta-analysis suggest that teicoplanin may not be inferior to vancomycin [6]. One meta-analysis noted a lower risk of nephrotoxicity with teicoplanin than with vancomycin [5].

Telavancin

Telavancin is a semisynthetic lipoglycopeptide that inhibits cell wall synthesis and disrupts cell membrane permeability [7]. The lipophilic side chain of telavancin confers enhanced potency, with approximately 10-fold more potency than vancomycin. It is bactericidal against MRSA, vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant S. aureus (VRSA). It has a half-life of seven to nine hours, permitting once daily dosing. Telavancin should be avoided in patients at risk for nephrotoxicity.

Telavancin was approved in November 2009 in the United States for the treatment of acute bacterial skin and skin structure infections (ABSSSI), and in June 2013 in US for hospital-acquired pneumonia (HAP) caused by gram-positive pathogens including MRSA where alternative treatments are not suitable.

Telavancin may prove effective for treatment of MRSA bacteremia. In a phase 2 trial of telavancin for treatment of bacteremia including 17 patients, cure rates were comparable for telavancin and standard therapy (88 vs 89%) [8]. A phase 3, multicenter, randomized, open-label, noninferiority trial of telavancin versus standard IV therapy in the treatment of patients with S. aureus bacteremia and right-sided infective endocarditis is ongoing [9]. This agent is an alternative when other options are not available.

Daptomycin

Daptomycin is a lipopeptide class antibiotic that disrupts cell membrane function via calcium-dependent binding, resulting in bactericidal activity in a concentration-dependent fashion. It is active against methicillin- and vancomycin –resistant staphylococci. It is the only new antibiotic that has a licensing indication for the treatment of S. aureus bacteremia (SAB) and right-sided endocarditis at 6 mg/kg/day [10]. It has the advantage of being a once-daily dosed, rapidly bactericidal agent. However, it lacks efficacy in pneumonia owing to its inactivation by pulmonary surfactant and it can cause muscle toxicity, so requires serum creatine kinase monitoring [11].

Daptomycin is currently the only antibiotic to have shown noninferiority to vancomycin in the treatment of MRSA bacteremia. A study comparing daptomycin versus initial low-dose gentamicin plus either an anti-staphylococcal penicillin or vancomycin in 124 patients with SAB and endocarditis demonstrated that daptomycin was not inferior to standard therapy [10]. Clinical success was low in the MRSA subset of patients but favored daptomycin (20 out of 45; 44.4%) over standard therapy (14 out of 44; 31.8%). However, five MRSA patients in the daptomycin group, most of whom had deep-seated infections or left-sided endocarditis, had microbiological failure with emergence on therapy of isolates with reduced daptomycin susceptibility (MIC increased from 0.25-0.5 to 2-4 μg/ml).

Daptomycin is an acceptable alternative to vancomycin for treatment of MRSA bacteremia. Historically, daptomycin has been used as salvage therapy in patients failing vancomycin therapy, particularly with high vancomycin MIC infections, but increasingly it is being used as initial therapy in high inoculum MRSA infections. A recent case-control study showed a possible advantage of daptomycin over vancomycin in infections caused by isolates with elevated vancomycin MIC [12]. Murray and colleagues reported 85 patients with MRSA bacteremia due to isolates with vancomycin MICs ≥1.5 μg/mL whose therapy was switched to daptomycin (median dose 8.4 mg/kg/d after median of 1.7 days of vancomycin) and compared their outcomes to 85 matched historical controls treated only with vancomycin (median trough 17.6 μg/mL). Patients treated with daptomycin experienced less frequent clinical failure and had a lower 30-day mortality. Limitations of this study were use of non-contemporaneous, historical vancomycin “control” group, and a much higher rate of infectious diseases consultation, which has been shown to improve outcomes in the daptomycin group [13].

Prior therapy with vancomycin, intermediate susceptibility to vancomycin (i.e. VISA) and retained prosthetic devices have been associated with an increased risk of daptomycin resistance. This is reflected in the Infectious Diseases Society of America guidelines for treatment of MRSA infections, where daptomycin dosing is recommended at 8 to 10 mg/kg for complicated bacteremia and in combination with other agents if there has been prior vancomycin treatment failure [1]. Laboratory data suggest that the administration of daptomycin in higher than approved doses may be superior to lower doses in terms of efficacy and reducing the risk of selection of resistance, but clinical data to support this hypothesis are largely lacking. Daptomycin resistance and cross-resistance in the setting of reduced vancomycin susceptibility raises concerns about widespread use of this agent.

Ceftaroline

Ceftaroline is a fifth-generation cephalosporin with bactericidal activity against MRSA and VISA as well as Gram-negative pathogens [14]. Ceftaroline fosamil, the pro-drug of ceftaroline, received approval by the US Food and Drug Administration (FDA) in 2010. The activity of ceftaroline against MRSA is the result of its high affinity for penicillin-binding proteins, but especially to an allosteric site of PBP2a near the transpeptidase domain. Binding to this site causes a conformational changes that opens the active site of the molecule, allowing binding of a second ceftaroline molecule with consequent inhibition of its enzymatic activity [15]. Ceftaroline is active in vitro against VISA and heterogeneous VISA (hVISA), as well as VRSA, and exhibits a “see-saw” effect in which there is an inverse correlation between the MICs of ceftaroline and vancomycin [16].

Ceftaroline has been approved for use in the treatment of ABSSSI and community-acquired pneumonia (CAP). In a phase 4 registry study of S. aureus bacteremia secondary to either bacterial SSTIs or to community-acquired bacterial pneumonia, clinical success in those with MRSA infection was reported in 18 of 32 [17]. Data for use of ceftaroline for treatment of MRSA bacteremia are limited to small retrospective case series.

In one study, ceftaroline therapy was reported to achieve clinical success in 101 of the 129 patients with SAB, 92% of whom had endocarditis [18]. For many patients, however, ceftaroline was administered together with a second antibiotics. Ceftaroline in combination with a second agent, most commonly daptomycin, has been effective as a salvage regimen in patients with persistent MRSA bacteremia.

Oxazolidinones

Linezolid is a bacteriostatic oxazolidinone that inhibits initiation of protein synthesis at the 50S ribosome [19]. This drug class may have enhanced efficacy against strains producing toxins such as Panton-Valentine leukocidin, α-hemolysin, and toxic shock syndrome toxin 1[20]. Unlike vancomycin, linezolid achieves high levels in the epithelial lining fluid of the lungs, making it a promising candidate for treatment of patients with HAP, including MRSA.

Linezolid has been compared with vancomycin for SAB in several case series and observational cohorts [21]. In a prospective open randomized trial, clinical success at test of cure was achieved in 19 of 24 (79.2%) linezolid recipients and 16 of 21 (76.2%) of those given vancomycin [22]. In patients with persistent (≥7 days) MRSA bacteremia while receiving vancomycin for at least 5 days, a switch to linezolid therapy led to similar outcomes as seen in those in whom vancomycin was continued [23]. Linezolid resistance and linezolid failure have been described [24]. Thus, an increasing frequency of resistance may potentially accompany more widespread use of this drug.

Tedizolid, the second drug of oxazolidinones, has key structural differences that allow additional target binding site interactions, accounting for its greater potency (2- to 8-fold lower MICs than linezolid against staphylococci) [25]. The FDA approved tedizolid in 2014 for use in acute bacterial SSTI caused by susceptible organisms, including MRSA. Published information regarding the use of tedizolid for the treatment of bacteremia is exceedingly limited. Like linezolid, tedizolid is bacteriostatic, making its use in endocarditis problematic. When administered in a dose consistent with human exposure, tedizolid exerted only a modest bactericidal effect that was inferior to both vancomycin and daptomycin in a rabbit model of experimental endocarditis, a result similar to that previously observed with linezolid [26]. Further study of tedizolid for treatment of MRSA bacteremia is needed.

Tigecycline

The first of a new generation of tetracyclines, glycylcyclines, tigecycline inhibits bacterial protein synthesis. Tigecycline’s distinctive feature is that it confers broad antibiotic coverage of drug-resistant Gram-positive bacteria and certain, but not all, species of multidrug-resistant Gram-negative bacteria, although it is a bacteriostatic agent.

There are substantial clinical trial data available on the use of tigecycline for intra-abdominal infections, complicated ABSSSIs, and nosocomial pneumonia, but there are insufficient data available specifically assessing the role of tigecycline in invasive MRSA infections. The use of tigecycline in bacteremia is controversial because of its low serum levels with standard dosing [27]. In a pooled, retrospective data analysis of phase 2 clinical trials, 91 patients being treated with tigecycline had secondary bacteremia detected. In the subset of patients with S. aureus infection (n=10), cure rates were 83.3% and 75% in the tigecycline and comparator arms, respectively [28]. The paradox of higher mortality and lower cure despite excellent in vitro activity is thought to be due to PK/PD considerations including high protein binding, an inadequate AUC/MIC with standard dosing, poor serum concentrations, and penetration into some tissues [29].

Combination Therapy

1. Combination with Vancomycin

Synergistic interactions between vancomycin and a wide variety of β-lactams, have been demonstrated in vitro. The mechanisms for this synergy are not clear but may include β-lactam induced potentiation of host defense peptide activity against S. aureus, and a “see-saw” effect whereby reduced vancomycin susceptibility results in reduced transcription of mecA and increased susceptibility to β-lactams. A retrospective study found a higher rate of clearance of MRSA bacteremia in patients receiving empiric vancomycin plus a β-lactam than in patients receiving vancomycin alone [30]. A pilot randomized clinical trial comparing an antistaphylococcal β-lactam in combination with vancomycin to vancomycin alone found that the duration of MRSA bacteremia was shorter by about a day 3.00 days with vancomycin alone versus 1.94 days with the combination [31]. There is a lack of evidence of benefit of vancomycin combined with other antistaphylococcal antibiotics. In a retrospective study, 35 patients with persistent (≥7 days) MRSA bacteremia while receiving vancomycin had their therapy altered. In 12 cases, vancomycin was continued, with an aminoglycoside added in 6, rifampin in 4, and both an aminoglycoside and a rifampin added in 2, but bacteremia cleared within 72 hours in only 2 (17%) [21].

2. Combination with Daptomycin

The combination of daptomycin and β–lactam enhances killing against daptomycin-susceptible and daptomycin-nonsusceptible MRSA, increases daptomycin binding to the bacterial cell membrane, and prevents the development of daptomycin resistance. Experiments in the rabbit model of endocarditis caused by a daptomycin-nonsusceptible strain of MRSA have shown that the combination of daptomycin of daptomycin with β–lactam reduced bacterial densities in all tissues compared to single agents [32]. Case reports describe the successful clearance of persistent bacteremia caused by MRSA strains, including strains that are nonsusceptible to daptomycin [33].

Summary

Treatment of MRSA bacteremia requires prompt source control and initiation of active antimicrobial therapy. Vancomycin remains the initial antibiotic of choice for the treatment of patients with MRSA bacteremia and endocarditis due to isolates with vancomycin MIC≤2 μg/mL. Daptomycin is an effective, although more costly alternative, and ceftaroline appears promising. Although often attributed to antibiotic failure, persistent MRSA bacteremia more often is dues to inadequate poor source control of foci of infection. The optimal salvage regimen for persistent MRSA bacteremia is uncertain. Treatment options for persistent MRSA bacteremia or bacteremia due to VISA or VRSA include daptomycin, ceftaroline, and combination therapies.

The need for antibiotics that are more efficacious than vancomycin has never been greater. Fortunately, several agents have become available for the treatment of MRSA. Compelling evidence of the improved efficacy of the newer agents against MRSA infections complicated by bacteremia in prospective, randomized, double-blind studies is lacking and even in observational studies the total number of MRSA is relatively small. The exact role and choice of agent needs to be defined.

Footnotes

Conflict of Interest: No conflicts of interest.

References

1. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ, Kaplan SL, Karchmer AW, Levine DP, Murray BE. J Rybak M, Talan DA, Chambers HF; Infectious Diseases Society of America. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011;52:e18–55. [PubMed] [Google Scholar]2. Kalil AC, Van Schooneveld TC, Fey PD, Rupp ME. Association between vancomycin minimum inhibitory concentration and mortality among patients with Staphylococcus aureus bloodstream infections: a systematic review and meta-analysis. JAMA. 2014;312:1552–1564. [PubMed] [Google Scholar]3. Neely MN, Youn G, Jones B, Jelliffe RW, Drusano GL, Rodvold KA, Lodise TP. Are vancomycin trough concentrations adequate for optimal dosing? Antimicrob Agents Chemother. 2014;58:309–316. [PMC free article] [PubMed] [Google Scholar]4. Zelenitsky S, Rubinstein E, Ariano R, Iacovides H, Dodek P, Mirzanejad Y, Kumar A, Cooperative Antimicrobial Therapy of Septic Shock-CATSS Database Research Group Vancomycin pharmacodynamics and survival in patients with methicillin-resistant Staphylococcus aureus-associated septic shock. Int J Antimicrob Agents. 2013;41:255–260. [PubMed] [Google Scholar]5. Cavalcanti AB, Goncalves AR, Almeida CS, Bugano DD, Silva E. Teicoplanin versus vancomycin for proven or suspected infection. Cochrane Database Syst Rev. 2010:CD007022. [PubMed] [Google Scholar]6. Yoon YK, Park DW, Sohn JW, Kim HY, Kim YS, Lee CS, Lee MS, Ryu SY, Jang HC, Choi YJ, Kang CI, Choi HJ, Lee SS, Kim SW, Kim SI, Kim ES, Kim JY, Yang KS, Peck KR, Kim MJ. Multicenter prospective observational study of the comparative efficacy and safety of vancomycin versus teicoplanin in patients with health care-associated methicillin-resistant Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2014;58:317–324. [PMC free article] [PubMed] [Google Scholar]7. Karlowsky JA, Nichol K, Zhanel GG. Telavancin: mechanisms of action, in vitro activity, and mechanisms of resistance. Clin Infect Dis. 2015;61(Suppl 2):S58–68. [PubMed] [Google Scholar]8. Stryjewski ME, Lentnek A, O’Riordan W, Pullman J, Tambyah PA, Miró JM, Fowler VG, Jr, Barriere SL, Kitt MM, Corey GR. A randomized Phase 2 trial of telavancin versus standard therapy in patients with uncomplicated Staphylococcus aureus bacteremia: the ASSURE study. BMC Infect Dis. 2014;14:289. [PMC free article] [PubMed] [Google Scholar]10. Fowler VG, Jr, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, Levine DP, Chambers HF, Tally FP, Vigliani GA, Cabell CH, Link AS, DeMeyer I, Filler SG, Zervos M, Cook P, Parsonnet J, Bernstein JM, Price CS, Forrest GN, Fätkenheuer G, Gareca M, Rehm SJ, Brodt HR, Tice A, Cosgrove SE. S. aureus Endocarditis and Bacteremia Study Group. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus
. N Engl J Med. 2006;355:653–665. [PubMed] [Google Scholar]11. Carpenter CF, Chambers HF. Daptomycin: another novel agent for treating infections due to drug-resistant gram-positive pathogens. Clin Infect Dis. 2004;38:994–1000. [PubMed] [Google Scholar]12. Moore CL, Osaki-Kiyan P, Haque NZ, Perri MB, Donabedian S, Zervos MJ. Daptomycin versus vancomycin for bloodstream infections due to methicillin-resistant Staphylococcus aureus with a high vancomycin minimum inhibitory concentration: a case-control study. Clin Infect Dis. 2012;54:51–58. [PubMed] [Google Scholar]13. Murray KP, Zhao JJ, Davis SL, Kullar R, Kaye KS, Lephart P, Rybak MJ. Early use of daptomycin versus vancomycin for methicillin-resistant Staphylococcus aureus bacteremia with vancomycin minimum inhibitory concentration >1 mg/L: a matched cohort study. Clin Infect Dis. 2013;56:1562–1569. [PubMed] [Google Scholar]14. Saravolatz LD, Stein GE, Johnson LB. Ceftaroline: a novel cephalosporin with activity against methicillin-resistant Staphylococcus aureus
. Clin Infect Dis. 2011;52:1156–1163. [PubMed] [Google Scholar]15. Otero LH, Rojas-Altuve A, Llarrull LI, Carrasco-López C, Kumarasiri M, Lastochkin E, Fishovitz J, Dawley M, Hesek D, Lee M, Johnson JW, Fisher JF, Chang M, Mobashery S, Hermoso JA. How allosteric control of Staphylococcus aureus penicillin binding protein 2a enables methicillin resistance and physiological function. Proc Natl Acad Sci USA. 2013;110:16808–16813. [PMC free article] [PubMed] [Google Scholar]16. Espedido BA, Jensen SO, van Hal SJ. Ceftaroline fosamil salvage therapy: an option for reduced-vancomycin-susceptible MRSA bacteraemia. J Antimicrob Chemother. 2015;70:797–801. [PubMed] [Google Scholar]17. Vazquez JA, Maggiore CR, Cole P, Smith A, Jandourek A, Friedland HD. Ceftaroline fosamil for the treatment of Staphylococcus aureus bacteremia secondary to acute bacterial skin and skin structure infections or community-acquired bacterial pneumonia. Infect Dis Clin Pract. 2015;23:39–43. [Baltim Md] [PMC free article] [PubMed] [Google Scholar]18. Casapao AM, Davis SL, Barr VO, Klinker KP, Goff DA, Barber KE, Kaye KS, Mynatt RP, Molloy LM, Pogue JM, Rybak MJ. Large retrospective evaluation of the effectiveness and safety of ceftaroline fosamil therapy. Antimicrob Agents Chemother. 2014;58:2541–2546. [PMC free article] [PubMed] [Google Scholar]19. Moellering RC. Linezolid: the first oxazolidinone antimicrobial. Ann Intern Med. 2003;138:135–142. [PubMed] [Google Scholar]20. Stevens DL, Wallace RJ, Hamilton SM, Bryant AE. Successful treatment of staphylococcal toxic shock syndrome with linezolid: a case report and in vitro evaluation of the production of toxic shock syndrome toxin type 1 in the presence of antibiotics. Clin Infect Dis. 2006;42:729–730. [PubMed] [Google Scholar]21. Jang HC, Kim SH, Kim KH, Kim CJ, Lee S, Song KH, Jeon JH, Park WB, Kim HB, Park SW, Kim NJ, Kim EC, Oh MD, Choe KW. Salvage treatment for persistent methicillin-resistant Staphylococcus aureus bacteremia: efficacy of linezolid with or without carbapenem. Clin Infect Dis. 2009;49:395–401. [PubMed] [Google Scholar]22. Wilcox MH, Tack KJ, Bouza E, Herr DL, Ruf BR, Ijzerman MM, Croos-Dabrera RV, Kunkel MJ, Knirsch C. Complicated skin and skin-structure infections and catheter-related bloodstream infections: noninferiority of linezolid in a phase 3 study. Clin Infect Dis. 2009;48:203–212. [PubMed] [Google Scholar]23. Park HJ, Kim SH, Kim MJ, Lee YM, Park SY, Moon SM, Park KH, Chong YP, Lee SO, Choi SH, Woo JH, Kim YS. Efficacy of linezolid-based salvage therapy compared with glycopeptide-based therapy in patients with persistent methicillin-resistant Staphylococcus aureus bacteremia. J Infect. 2012;65:505–512. [PubMed] [Google Scholar]24. Sánchez García M, De la Torre MA, Morales G, Peláez B, Tolón MJ, Domingo S, Candel FJ, Andrade R, Arribi A, García N, Martínez Sagasti F, Fereres J, Picazo J. Clinical outbreak of linezolid-resistant Staphylococcus aureus in an intensive care unit. JAMA. 2010;303:2260–2264. [PubMed] [Google Scholar]25. Rybak JM, Marx K, Martin CA. Early experience with tedizolid: clinical efficacy, pharmacodynamics, and resistance. Pharmacotherapy. 2014;34:1198–1208. [PubMed] [Google Scholar]26. Chan LC, Basuino L, Dip EC, Chambers HF. Comparative efficacies of tedizolid phosphate, vancomycin, and daptomycin in a rabbit model of methicillin-resistant Staphylococcus aureus endocarditis. Antimicrob Agents Chemother. 2015;59:3252–3256. [PMC free article] [PubMed] [Google Scholar]27. Stein GE, Babinchak T. Tigecycline: an update. Diagn Microbiol Infect Dis. 2013;75:331–336. [PubMed] [Google Scholar]28. Gardiner D, Dukart G, Cooper A, Babinchak T. Safety and efficacy of intravenous tigecycline in subjects with secondary bacteremia: pooled results from 8 phase III clinical trials. Clin Infect Dis. 2010;50:229–238. [PubMed] [Google Scholar]29. Ramirez J, Dartois N, Gandjini H, Yan JL, Korth-Bradley J, McGovern PC. Randomized phase 2 trial to evaluate the clinical efficacy of two high-dosage tigecycline regimens versus imipenem-cilastatin for treatment of hospital-acquired pneumonia. Antimicrob Agents Chemother. 2013;57:1756–1762. [PMC free article] [PubMed] [Google Scholar]30. Dilworth TJ, Ibrahim O, Hall P, Sliwinski J, Walraven C, Mercier RC. beta-Lactams enhance vancomycin activity against methicillin-resistant Staphylococcus aureus bacteremia compared to vancomycin alone. Antimicrob Agents Chemother. 2014;58:102–109. [PMC free article] [PubMed] [Google Scholar]31. Davis JS, Sud A, O’Sullivan MV, Robinson JO, Ferguson PE, Foo H, van Hal SJ, Ralph AP, Howden BP, Binks PM, Kirby A, Tong SY.
Combination Antibiotics for MEthicillin Resistant Staphylococcus aureus (CAMERA) study group; Australasian Society for Infectious Diseases Clinical Research Network. Combination of vancomycin and beta-lactam therapy for methicillin-resistant Staphylococcus aureus bacteremia: a pilot multicenter randomized controlled trial. Clin Infect Dis. 2016;62:173–180. [PubMed] [Google Scholar]32. Chambers HF, Basuino L, Hamilton SM, Choo EJ, Moise P. Daptomycin- β-lactam combinations in a rabbit model of daptomycin-nonsusceptible methicillin-resistant Staphylococcus aureus endocarditis. Antimicrob Agents Chemother. 2016;60:3976–3979. [PMC free article] [PubMed] [Google Scholar]33. Sakoulas G, Moise PA, Casapao AM, Nonejuie P, Olson J, Okumura CY, Rybak MJ, Kullar R, Dhand A, Rose WE, Goff DA, Bressler AM, Lee Y, Pogliano J, Johns S, Kaatz GW, Ebright JR, Nizet V. Antimicrobial salvage therapy for persistent staphylococcal bacteremia using daptomycin plus ceftaroline. Clin Ther. 2014;36:1317–1333. [PubMed] [Google Scholar]

MRSA – NHS

MRSA is a type of bacteria that’s resistant to several widely used antibiotics. This means infections with MRSA can be harder to treat than other bacterial infections.

The full name of MRSA is methicillin-resistant Staphylococcus aureus. You might have heard it called a “superbug”.

MRSA infections mainly affect people who are staying in hospital. They can be serious, but can usually be treated with antibiotics that work against MRSA.

How you get MRSA

MRSA lives harmlessly on the skin of around 1 in 30 people, usually in the nose, armpits, groin or buttocks. This is known as “colonisation” or “carrying” MRSA.

You can get MRSA on your skin by:

• touching someone who has it
• sharing things like towels, sheets and clothes with someone who has MRSA on their skin
• touching surfaces or objects that have MRSA on them

Getting MRSA on your skin will not make you ill, and it may go away in a few hours, days, weeks or months without you noticing. But it could cause an infection if it gets deeper into your body.

People staying in hospital are most at risk of this happening because:

• they often have a way for the bacteria to get into their body, such as a wound, burn, feeding tube, drip into a vein, or urinary catheter
• they may have other serious health problems that mean their body is less able to fight off the bacteria
• they’re in close contact with a large number of people, so the bacteria can spread more easily

Healthy people, including children and pregnant women, are not usually at risk of MRSA infections.

Symptoms of MRSA

Having MRSA on your skin does not cause any symptoms and does not make you ill.

You will not usually know if you have it unless you have a screening test before going into hospital.

If MRSA gets deeper into your skin, it can cause:

• swelling
• warmth
• pain
• pus
• redness, but this may be less visible on darker skin

If it gets further into your body, it can also cause:

Tell a member of staff if you get these symptoms while in hospital.

Call a GP or NHS 111 if you get these symptoms outside of hospital.

Screening and testing for MRSA

If you need to go into hospital and it’s likely you’ll be staying overnight, you may have a simple screening test to check your skin for MRSA before you’re admitted.

This is normally done at a pre-admission clinic or a GP surgery. A nurse will run a cotton bud (swab) over your skin so it can be checked for MRSA.

Swabs may be taken from several places, such as your nose, throat, armpits, groin or any damaged skin. This is painless and only takes a few seconds.

The results will be available within a few days.

If you’re not carrying MRSA, it’s unlikely you’ll be contacted about the result and you should follow the instructions from the hospital.

If you’re carrying MRSA, you’ll be told by the hospital or a GP.

You may need treatment to remove the bacteria to reduce your risk of getting an infection or spreading the bacteria.

Treatments for MRSA

Removing MRSA from your skin

If screening finds MRSA on your skin, you may need treatment to remove it. This is known as decolonisation.

This usually involves:

• applying antibacterial cream inside your nose 3 times a day for 5 days
• washing with an antibacterial shampoo every day for 5 days
• changing your towel, clothes and bedding every day during treatment – the laundry should be washed separately from other people’s and at a high temperature

Treatment is normally done at home, but may be started after going into hospital if you need to be admitted quickly.

Treatment for an MRSA infection

If you get an MRSA infection, you’ll usually be treated with antibiotics that work against MRSA.

These may be taken as tablets or given as injections. Treatment can last a few days to a few weeks.

During treatment, you may need to stay in your own room or in a ward with other people who have an MRSA infection to help stop it spreading.

You can normally still have visitors, but it’s important they take precautions to prevent MRSA spreading.

Preventing MRSA

If you’re staying in hospital, there are some simple things you can do to reduce your risk of getting or spreading MRSA.

You should:

• wash your hands often (hand wipes and alcohol hand gel are also effective) – especially before and after eating and after going to the toilet
• follow the advice you’re given about wound care and looking after devices that could lead to infection (such as urinary catheters or drips)
• report any unclean facilities to staff – do not be afraid to talk to staff if you’re concerned about hygiene

If you’re visiting someone in hospital, clean your hands before and after entering the ward and before touching the person.  Gel or wipes are often placed by patients’ beds and at the entrance to wards.

It’s also a good idea to put a dressing over any breaks in your skin, such as sores or cuts, to stop MRSA getting into your body.

Get more advice about visiting someone in hospital

Video: MRSA

This video explains how MRSA is caught, what happens when you have it and how to prevent infection.

Media last reviewed: 12 January 2021
Media review due: 12 January 2024

Page last reviewed: 24 March 2020
Next review due: 24 March 2023

Learning about MRSA: A guide for Patients

On this page:
About MRSA
Transmission
Diagnosis
Treatment
Preventing the Spread
Caring for Yourself
Laundry
Cleaning
Changing Bandages
Important Note

About MRSA

What is MRSA and why is it so serious?

• Staphylococci or “staph” bacteria commonly live on the skin and in the nose. Usually, staph bacteria don’t cause any harm.
• However,if they get inside the body they can cause an infection.
• When common antibiotics don’t kill the staph bacteria, it means the bacteria have become resistant to those antibiotics.
• This type of staph is called MRSA (Methicillin-Resistant Staphylococcus aureus).
• MRSA was first identified in the 1960’s and was mainly found in hospitals and nursing homes.
• In the late 1990’s, a new type of MRSA was identified.
• This type of MRSA is becoming more common among children and adults who do not have medical conditions.

What does MRSA look like?

Most often, MRSA causes infections on the skin. These infections may look like any one of the following:

• Large, red, painful bumps under the skin (called boils or abscesses)
• A cut that is swollen, hot and filled with pus
• Blisters filled with pus (called impetigo)
• Sores that look and feel like spider bites (However, MRSA is not caused by a spider bite or any other insect bite. )

It is also possible to have MRSA in other areas of the body, such as blood, lungs, joints, eyes, and urine. These types of infections are less common, although they can be more serious. Because skin infections are the most common, this booklet will focus on them.

MRSA Transmission

How did I get MRSA?

• Anyone can get MRSA. You can get MRSA by touching someone or something that has the bacteria on it and then touching your skin or your nose.

Some ways that you could get MRSA:

• Touching the infected skin of someone who has MRSA
• Using personal items of someone who has MRSA, such as towels, wash cloths, clothes or athletic equipment
• Touching objects, such as public phones or door knobs, that have MRSA bacteria on the surface and then touching your nose or an open sore, paper cut, etc.

You may increase your chances of getting MRSA if:

• You take antibiotics a lot
• You take antibiotics without a prescription
• You don’t follow your doctor’s directions when taking antibiotics (for example you stop taking your antibiotics before finishing a prescription or you skip doses)
• You frequently get cuts or scrapes on your skin (Your skin serves as a barrier to infection. When the skin gets damaged staph bacteria can enter and increase your risk for infection.)

There are two ways you can have MRSA.

1. You can have an active infection. An active infection means you have symptoms. This is usually a boil, a sore, or an infected cut that is red, swollen, or pus-filled.
2. You can be a carrier. If you are a carrier you do not have symptoms that you can see, but you still have MRSA bacteria living in your nose or on your skin. If you are a carrier, your doctor may say that you are colonized. These words – “carrier” and “colonized” – mean the same thing.

MRSA Diagnosis

Will I always have MRSA?

• Many people with active infections are treated effectively, and no longer have MRSA.
• However, sometimes MRSA goes away after treatment and comes back several times.
• If MRSA infections keep coming back again and again, your doctor can help you figure out the reasons you keep getting them.

If I have MRSA, do I need to do anything special when I go to a clinic or hospital?

• If you have ever had an active MRSA infection or you are a carrier, you should tell your health care providers.
• They will wash their hands and wear gloves when caring for you.
• They may also wear a gown over their clothes and may wear a mask.
• If you are staying in a hospital or nursing home, a “Special Precautions” card may be put on the door of your room.
• This card alerts staff to use extra care to prevent the spread of MRSA.
• Your visitors may be instructed to avoid touching infected skin and to take other precautions such as wearing gloves or gowns when visiting you.

Is there a test for MRSA?

• You would not usually be tested for MRSA unless you have an active infection. If you have a skin infection, your doctor may take a sample of the area to find out what bacteria is causing your infection. This is called taking a culture. The lab will then test the bacteria to find out which antibiotic is best for you. If your MRSA infections keep coming back again and again, your doctor may test you and your family members to see if you are carriers. In this case, the doctor would take a culture from the nose or other areas where MRSA can be found.

Treating MRSA

How is MRSA treated?

• MRSA should always be treated by a doctor. It is important to follow the instructions for treatment that your doctor gives you.

If you have an active MRSA infection, your doctor may choose one or more of the following treatments:

1. Give antibiotics
2. Drain the infection
3. Reduce the amount of staph on your skin and in your nose

1. Give antibiotics

MRSA is resistant to many antibiotics so it can be difficult to treat. However, there are antibiotics that can treat MRSA and make the infection go away. Your doctor may culture your infection and have the lab test the bacteria to find out which antibiotic is best for you. If your doctor gives you antibiotics, take them exactly as prescribed. Do not stop early, even if you feel better or if your infection looks healed. The last few pills kill the toughest germs. Never take antibiotics without a prescription from your doctor.

2. Drain the infection

Don’t do this yourself. It is very dangerous to squeeze or poke a skin infection because it can push the bacteria deeper into the skin and make the infection much worse. Your doctor will open the sore and drain it. After the infection is drained, you must keep it covered with a clean, dry bandage, until it heals

3. Reduce the amount of staph on your skin or in your nose

This may prevent the spread of MRSA if you have an active infection or if you are a carrier.

To decrease the amount of staph on your body your doctor may, for a short period of time:

• Tell you to shower daily with antibacterial soap
• Prescribe antibiotic ointment to put in your nose for several days
• Prescribe antibiotic pills (in some cases)

Contact your doctor if:

• you have any new symptoms during or after treatment for a MRSA skin infection such as a new fever or a fever that won’t go away
• the infection gets worse
• the infection is not healing
• the infection comes back
• you have questions

Preventing the Spread of MRSA

What can I do to prevent spreading my infection to others?

• Clean your hands often with soap and water or an alcohol-based hand sanitizer
• Take a bath or shower often, be sure to use soap to clean your body while showering or bathing
• Wash your sheets and towels at least once a week
• Change your clothes daily and wash them before wearing again
• Do not share towels, wash cloths, razors, or other personal items
• If you get a cut or scrape on your skin, clean it with soap and water and then cover it with a bandage
• Do not touch sores; if you do touch a sore, clean your hands right away
• Cover any infected sores with a bandage and clean your hands right away after putting on the bandage
• Wear clothes that cover your bandages and sores, if possible
• Clean frequently used areas of your home (bathrooms, countertops, etc.) daily with a household cleaner
• Do not participate in contact sports until your sores have healed
• Do not go to a public gym, sauna, hot tub or pool until sores have healed

Caring for Yourself

Does it matter how I wash my hands?

• Yes. You have to rub your hands for at least 20 seconds to get rid of the bacteria.

How do I clean my hands with alcohol-based hand sanitizer?

• Use enough to cover all the surfaces of your hands.

Clean Your Hands! Poster
This 11×17 poster shows the six steps for washing hands with soap and water or two for cleaning with alcohol-based hand sanitizers.

Laundry

Do I need to be careful when I do laundry?

Yes. Dirty clothes and bedding can spread MRSA bacteria.

• When touching your laundry or changing your sheets, hold the dirty laundry away from your body and clothes to prevent bacteria from getting on your clothes
• Wear disposable gloves to touch laundry that is soiled with body fluids, like drainage from a sore, urine or feces
• Immediately put the laundry into the washer or into a plastic bag until it can be washed
• Wash your laundry with warm or hot water, use bleach if possible
• Dry in a warm or hot dryer and make sure the clothes are completely dry
• Clean your hands after touching dirty sheets or clothing and before touching clean laundry, even if you have been wearing gloves
• Throw gloves away after taking them off (do not reuse them) and clean your hands

How often should I change clothes and bedding?

• Change your sheets and towels at least once a week
• Change your clothes daily
• Do not put dirty clothes or clothes you have just worn back in your closet or drawers until they have been washed

Cleaning

What about cleaning my house?

• Use a household disinfectant or bleach solution to clean surfaces daily
• Pay attention to items that are frequently touched – light switches, doorknobs, phones, toilets, sinks, tubs and showers and kitchen counters
• Wipe the surface or object with the disinfectant and let it dry

Disinfectants to use:

• You can use any cleaner you buy at the grocery store that has the word “disinfectant” on it, remember to read the label and follow the directions
• Make your own solution of bleach and water:
  • Mix two teaspoons bleach into one quart of water in a spray bottle and label it “bleach solution”
  • Make it fresh each time you plan to clean because the bleach evaporates out of the water making it less effective
  • Never mix bleach with other cleaners, especially ammonia
  • Keep the bleach solution away from children and don’t put it in bottles that could be mistaken for something to drink

How often should I clean?

• It is important that you clean daily. Especially items or surfaces you touch often.

Changing Bandages

Important Note:

• MRSA can cause serious infections that can become life-threatening if left untreated.
• If you or someone in your family has been diagnosed with MRSA, there are steps you should take to avoid spreading it to your family and friends.
• Follow the recommendations and practice good hygiene to take care of yourself.
• MRSA may cause physical pain and emotional stress, but keep in mind that it can be managed.

Things to remember about having MRSA:

• Clean your hands often
• Take care of yourself: eat right, exercise, quit smoking, and avoid stress
• Take good care of your skin
• Keep skin infections covered to avoid spreading MRSA to others
• Talk with your doctor if you have questions or concerns

90,000 Antibiotic therapy for methicillin-resistant Staphylococcus aureus (MRSA) in non-surgical wounds

Non-surgical wounds include chronic skin ulcers (such as pressure sores or diabetic ulcers), burns, and traumatic wounds. Methicillin-resistant (methicillin-resistant) Staphylococcus aureus (MRSA) can be present in 7-30% of these wounds, and MRSA can spread into the bloodstream and cause life-threatening illness. Wounds that have MRSA may have symptoms of infection such as redness, pain, and pus discharge.Having MRSA without signs of infection is called colonization. It is not clear whether antibiotics should be used when colonizing MRSA in nonsurgical wounds. It is also not clear which antibiotic should be used for MRSA-infected wounds. We tried to figure this out by performing a thorough search of the medical literature for studies that compared different antibiotic treatments for nonsurgical wounds infected or colonized with MRSA. We included only randomized controlled trials, i.e.Because, if done properly, they provide the best information. We included all relevant randomized controlled trials, regardless of language, year of publication, and number of people who participated in them. The two reviewers independently identified trials and extracted relevant information from them to reduce the likelihood of error during the process.

We found three trials that provide some information on this topic. A total of 47 people with infectious complications of diabetic foot caused by MRSA were randomized (randomly assigned) into six groups with different antibiotic therapy (treatment choice is determined by a method similar to a coin toss).The only reported outcome was eradication of MRSA. These clinical trials did not provide any other patient and health care outcomes such as death, quality of life, length of hospital stay, use of health care resources, and wound healing time. Each trial compared different antibiotics, and each comparison found no difference in the effectiveness of antibiotics to eradicate MRSA. The three trials were very small and had a number of design flaws, so it is still impossible to answer which antibiotic is most effective in eradicating MRSA from nonsurgical wounds.Since there have been no trials comparing antibiotic use versus no antibiotic therapy, we do not know if antibiotic use generally has an effect in people with non-surgical wounds colonized with MRSA. Further carefully designed randomized controlled trials are needed to determine the best treatment for nonsurgical wounds colonized or infected with methicillin-resistant Staphylococcus aureus (MRSA).

Methicillin-Resistant Staphylococcus aureus (MRSA) – Medical District of Southern Nevada

What is MRSA?

MRSA stands for methicillin-resistant Staphylococcus aureus, a bacterium that is resistant to most antibiotics commonly used for staphylococcal infections.These drugs include:

• Methicillin
• Oxacillin
• Nafcillin
• Cephalosporins
• Imipenem
• Other Beta-Lactams

What is a MRSA Reservoir?

MRSA can affect humans in two different ways:

• Colonization
• Infectious Disease

When a person carries bacteria on the skin or nose without showing signs or symptoms of infection, the person is considered colonized.

If a person has signs of an infection with MRSA, the person is considered infected.

Signs of MRSA infection include:

• Abscesses
• Infected infections
• Pneumonia
• Respiratory infections
• Blood, stool, or urinary tract infections

How does MRSA spread from person to person?

MRSA is most commonly spread from person to person through direct contact.For example, in healthcare settings, MRSA is most commonly spread from patient to patient by the hands of healthcare professionals.

How can you stop the spread of MRSA?

The single most effective way to prevent the spread of infection is through proper hand washing, i.e. washing with soap and water for at least 20 seconds and rinsing with warm running water. Hands should be washed both before and after contact with the patient.

Other measures include:

• Use protective equipment to avoid contact with body fluids of another person
• Gloves should be worn for all changes of clothing
• Protective equipment should be disposed of after use
• Hands should be washed after removing protective equipment
• Separate clean and dirty laundry

Follow a daily environmental cleaning schedule, including disinfecting handrails, IV stands and telephones.Follow your facility’s isolation procedures.

Is MRSA a bigger problem than other infections?

The answer is yes and no. MRSA is not a “super bug” and is no more virulent than Staphylococcus aureus. However, all infections are of interest to healthcare workers and patients.

MRSA is of particular importance because MRSA infections are very difficult to treat. Typically, MRSA infections are treated with an intravenous drug called vancomycin.The side effects of this drug can be quite serious, especially in elderly or immunocompromised patients.

In addition, patients with invasive devices such as catheters, nasogastric or gastrointestinal tubes, or intravenous lines are much more likely to acquire infections, including MRSA.

What can be done to prevent the spread of MRSA?

1. Inform the patient, if possible, of his / her condition.
2. Observe universal precautions. Keep drainage lesions covered.
3. Use standard cohorts to care for patients with MRSA if possible. If individual rooms are not available, select patients with MRSA. Make sure that a patient with an MRSA infection does not share a room with a patient prone to infection as described above.

Where can I get more information?

Contact the Director of the Southern Nevada Department of Nursing or Public Health, Office of Epidemiology at (702) 759-1300.

Comparative evaluation of the effectiveness of antibiotic therapy for MRSA – associated soft tissue infection in critically ill burned patients

V.V. KULABUKHOV , Candidate of Medical Sciences, Associate Professor, A.N. KUDRYAVTSEV, A.G. CHIZHOV , Institute of Surgery named after A.V. Vishnevsky Ministry of Health of Russia, Moscow

Intensive care units can now be considered as a high-risk area for developing nosocomial infections.Gram-positive microflora, especially in specialized surgical departments, can play one of the leading roles in the development of infectious complications of this group, which determine the severity of the patient’s condition, the length of stay in the intensive care unit and nosocomial mortality [13].

INTRODUCTION

Staphylococcus aureus (Staphylococcus aureus) is the second most important pathogen responsible for infectious complications associated with the fact of providing medical care.This pathogen is associated with 30% of cases of infection in the area of ​​surgical intervention, is isolated in 24% of patients with ventilator-associated pneumonia [7]. According to the multicenter study OASIS (2011), in northern and central Italy, 44% of cases of bacteremia were associated with gram-positive flora, of which 35.8% with various strains of Staphylococcus aureus [12]. Aureus strains with drug resistance to semi-synthetic penicillins (MRSA) have the greatest clinical significance.They are allocated in 49-65% of all cases of all nosocomial staphylococcal infections. As of 2007, there were 94,360 cases of MRSA-associated infections in the United States. During the year of observation, 18 650 deaths were recorded, determined by this infectious complication [10]. With regard to forms of localization of an infectious disease caused by MRSA, the most frequently observed are nosocomial pneumonia (34%), soft tissue infection (27%), and bloodstream infection (18%) [8]. In the event of the development of soft tissue infection in the areas of burn injury, according to S.V. Yakovleva, 2013, S. aureus is the most frequent pathogen – up to 40.4% of cases, 61.7% of patients have MRSA strains [2].

Staphylococcus aureus, including strains of MRSA, can asymptomatically colonize the skin of both patients, if they seek medical help, and medical personnel who provide this assistance. The most important loci of the human body in relation to colonization by Staphylococcus aureus are the skin and mucous membranes of the vestibule of the nasal cavity, the skin of the axillary cavities and the perineum.The period of colonization of MRSA can take quite a long time, on average 56 days, until the infection develops [8]. During this period, a person colonized with MRSA can pose a serious epidemiological hazard by spreading methicillin-resistant S. aureus strains in the environment. According to S.S. Huang, 2011 [8], 24% of patients who underwent an infectious disease associated with MRSA had a recurrence of infection during the year of follow-up, and in half of the patients in the first three months after discharge.The cited data on mortality of patients with identified MRSA colonization require special attention. The authors indicate that within one year after the discovery of MRSA, 46% of patients in this group died. More than one third of all deaths (35%, 94 of 269 patients) were directly attributable to MRSA infection. It is noteworthy that no clear relationship between mortality and the duration of the MRSA colonization period was found, as well as a relationship with the duration of hospitalization in these patients.

It should also be noted that the contact mechanism of MRSA spread is the main one in hospital settings. It is realized both directly during direct contacts between a patient or a carrier and a susceptible person, and in a household contact way, through contamination of environmental objects. In rare cases, it is possible to transmit infection by blood contact through contaminated medical equipment during diagnostic and treatment procedures. The facts of the development of resistance to semisynthetic penicillins during the time of S.aureus are very rare.

Similar features of MRSA infection explain the increased attention to this problem by a large number of clinicians. This is leading to the creation of programs to prevent the spread of methicillin-resistant S. aureus strains in health care facilities and in the “home” where regular outpatient care is provided or where a patient colonized with MRSA is discharged. These programs are based on preventive measures aimed at blocking the pathways of transmission of MRSA.The basic measures of these programs are not MRSA-specific and are aimed at effective prevention of all forms of nosocomial infections. With regard to narrowly targeted measures, it is necessary to highlight early recognition and isolation of carriers of MRSA, decolonization strategies, motivation of personnel alertness in relation to MRSA infection, improvement of microbiological diagnostics, epidemiological surveillance of carriers of MRSA, etc. Special attention should be paid to early etiotropic therapy in case of development acute form of MRSA infection.Taking into account the above circumstances, its tasks should also include the effective eradication of the pathogen from the patient’s body, preventing the formation of MRSA-carriage in convalescents.

In recent years, vancomycin has been used as the main etiotropic agent for the treatment of MRSA infection [3]. The essential features of the use of this antimicrobial agent are: predominantly bacteriostatic effect (a very low bactericidal activity can be achieved with the use of high doses of the drug), lack of activity in structured microbial communities, significant difficulties in selecting the optimal dose, poor tolerance and a high risk of adverse reactions when effective for dosage therapy.These circumstances complicate the eradication of MRSA during treatment with vancomycin [4], which hypothetically suggests the formation of MRSA carriage in survivors of the infection. Difficulties in the selection of optimal dosages of vancomycin are associated with the phenomenon of “creeping” minimum inhibitory concentration (“creep” MIC). The essence of this phenomenon is that during the use of an antibiotic in suboptimal doses, the sensitivity of MRSA to it decreases, which requires an increase in the amount of the drug administered. It is also a known fact that with an increase in the MIC of vancomycin for MRSA in the range between 1 and 2 μg / ml, an increase in the dosage of the drug can lead to an increase in its concentration in the blood serum of more than 20.8 mg / L.This greatly enhances the nephrotoxic effects of the antibiotic [9]. In addition, M.N. Jeffers et al (2007) noted that long-term vancomycin therapy, even at moderate concentrations, provokes the development of renal dysfunction. Thus, today’s reality compels us to include convalescents of MRSA infection who received vancomycin at risk of MRSA colonization. The peculiarities of the pharmacodynamic profile of the drug, low safety and poor tolerance of it in effective clinical dosages do not allow the use of vancomycin in the optimal concentration that can prevent this phenomenon.

The above circumstances determine the interest of clinicians and researchers in other drugs with activity against MRSA. Linezolid, tigecycline, and daptomycin are now the most common. Of the indicated drugs, only daptomycin has a bactericidal effect in therapeutically available dosages. The benefits of the antibiotic include the ability to penetrate structured microbial communities, such as biofilms, to create an effective concentration in infected tissues.The mechanism of antibacterial action is associated with a violation of the integrity of the cell wall of bacteria, which leads to their rapid death. The rate of eradication of MRSA depends on the concentration-dependent killing used. Currently, the highest dose of daptomycin is limited to 6 mg / kg, but in a clinical experiment, even higher doses (10-12 mg / kg) had an adequate safety profile, significantly reducing the time of MRSA eradication [6]. As well as for vancomycin, for daptomycin in research practice the phenomenon of “creeping” minimal inhibitory concentration (“creep” MIC) has been described [3], however, its development is easily overcome due to the significant therapeutic reserve associated with the possibility of safely increasing the dosage of the drug to the level of a satisfactory bactericidal activity.According to P. Lagace-Wiens et al (2011), no clinical confirmation of the MIC creep phenomenon for daptomycin was found [11]. Isolated cases of MRSA resistance to daptomycin have been associated with previous use of other antibiotics with anti-MRSA activity or during long-term use of the drug in an inappropriate dose [5]. The Food and Drug Administration (FDA) has approved daptomycin for the treatment of skin and soft tissue infections, bloodstream infections with bacteremia, and right-sided endocarditis.The Federal Service for Surveillance in Healthcare and Social Development (Roszdravnadzor) of the Russian Federation, in a message dated October 4, 2010, strongly recommends adhering to these indications for the use of daptomycin due to the risk of developing a number of adverse events (reversible eosinophilic pneumonia).

Thus, it seems rational to include daptomycin in the empiric therapy of soft tissue infection in areas of burn injury as a drug of choice that promotes rapid eradication of gram-positive pathogens (incl.h. MRSA) and allowing to prevent their further carriage in convalescents.

In order to analyze the rate of complete eradication of the pathogen when using various antibacterial agents with anti-MRSA activity for the treatment of invasive wound infection in burn areas, we undertook an observational retrospective cohort study. In the course of it, the medical histories of patients with severe burn injuries (Frank index more than 60 units) who were admitted to the intensive care unit of the Department of Thermal Injuries of the Institute of Surgery named after V.I.A.V. Vishnevsky in the period from November 2013 to February 2014 on the 7-10th days after the injury. The criterion for inclusion in the study was the presence in patients of invasive wound infection [1] associated with MRSA, in the complex therapy of which antibacterial drugs with anti-MRSA activity were used: Cubicin (Cubicin®, Novartis Pharmaceuticals UK, Ltd., Great Britain) active substance: daptomycin (daptomycin) and Vankorus® (Vancorus, JSC SINTEZ, Russia) active substance: vancomycin (vancomycin).

The exclusion criteria were the presence of allergic reactions to these drugs, the patient’s age was up to 18 years.

MATERIALS AND METHODS

The reason for transfer to a specialized ICU of the burn center of the Institute of Surgery named after A.V. Vishnevsky, all patients had a severe thermal injury (Frank index more than 60 units) with the development of burn disease at the stage of septicotoxemia, complicated by the course of invasive wound infection in the areas of burn injury.

All patients ( Table 1) , 12 people (3 women, 9 men, mean age 42 ± 17.3 years), at the time of transfer to the ICU, underwent complex therapy as recommended by the American Burn Association (ABA). In all observed cases, there was a prolonged wound infection in the areas of burn injury, the etiology of which was determined retrospectively.

In order to limit the pathogenic load from the areas of wound burn infection, all admitted patients underwent sanitizing surgical interventions.In the postoperative period, multicomponent intensive therapy was continued in the intensive care unit. All participants in the study received the necessary therapy, the main components of which were artificial ventilation of the lungs, infusion and transfusion therapy, and the use of anticoagulants. During their stay in the ICU, the patients underwent a comprehensive clinical, laboratory and instrumental examination with the registration of clinical, biochemical blood parameters, hemostasiogram; determination of acid-base parameters, gas composition of arterial and venous blood.

Before the start of antibiotic therapy, the patients underwent microbiological studies of the wound discharge. Subsequently, microbiological monitoring was carried out by cultural bacteriological analysis of the discharge of wounds every 48 hours, until the condition was stabilized and transferred from the department. Microbiological studies were performed in accordance with the standards of the Clinical and Laboratory Standards Institute (CLSI).

The prescription of antibacterial drugs was carried out according to the de-escalation scheme during the first 60 minutes of stay in the department, taking into account the previous inpatient treatment and previous data from microbiological studies.Vancomycin as a traditional antibacterial agent and daptomycin, which became available from the moment of its inclusion in the therapeutic practice of the Institute of Surgery, were used as etiotropic therapy for the presumed MRSA infection at the time of admission. Taking into account these circumstances, 6 patients (Vanco group) were selected who received VANCORUS® (VANCORUS) 1 g after 12 hours in the form of a slow intravenous infusion at a rate of no more than 10 mg / min for at least 60 minutes, and 6 patients ( Cubic group), who used CUBICIN® 6 mg / kg of the drug once a day, administered by intravenous infusion over 30 minutes.

The criteria for the effectiveness of the therapy were the timing of the eradication of MRSA according to the microbiological study of the wound discharge.

Statistical processing. For data analysis, a Microsoft Access database and archival materials were used. Statistical processing was performed using the STATISTICA 7.0 system (StatSoft, USA). Samples in the study were compared relative to mean values ​​using a nonparametric alternative to the t-test for independent groups (given the total number of observations in the study n <100) U - Mann - Whitney test.

RESULTS OF THE STUDY

At the time of connection to the monitor, the patients had a course of burn disease in the phase of septicotoxemia complicated by invasive wound infection in the areas of burn injury. In all patients in the study, positive results of microbiological analysis of wound discharge were obtained (Table 2 ). Microbial associations of gram-negative flora with methicillin-resistant staphylococcus were found. Fecal enterococcus was isolated in two cases; Candida albicans fungi were isolated from one patient.

The use of these antibacterial agents was not accompanied by adverse events in both groups of patients. During therapy, the patients showed no signs of renal failure.

The duration of specific anti-MRSA therapy in the Vanco group was longer than in the Cubic group ( Table 3 ). Despite this, it was possible to isolate an average of more than 20 days of observation from the wound discharge of patients of the Vanco MRSA group, which indicated a significantly longer persistence of methicillin-resistant S.aureus compared to the Cubic group.

In two patients of the Vanco group, MRSA continued to exude from the surface of residual burn skin defects after the relief of clinical signs of invasive wound infection and the transfer of the patient from the intensive care unit. MRSA was determined at a concentration of less than 105 CFU. This was considered as continued colonization, which predisposed to the formation of MRSA carriers during the recovery period of burn disease. Complete decontamination of the burn lesion zone was achieved in one patient on the 40th day, and in the other on the 48th day from the moment of admission to the department due to adequate toilet of the remaining skin defects with antiseptics with anti-MRSA activity.

Conclusion

Summarizing the above, it can be noted.

1. MRSA colonization is an additional risk factor for death in patients seeking medical care.
2. MRSA colonization may occur in convalescents of acute MRSA infection due to inadequate use of antibacterial agents with anti-MRSA activity.
3. The most general requirement for antibacterial agents used for the treatment of infection associated with methicillin-resistant strains of Staphylococcus aureus is rapid and effective eradication of the pathogen from the patient’s body, preventing the formation of MRSA-carriage in convalescent patients.
4. Daptomycin, included in the empirical therapy of soft tissue infection in the areas of burn injury, used in moderate therapeutic dosages, has advantages over vancomycin in terms of the rate of eradication of MRSA, prevents long-term persistence of the pathogen in this group of patients.

Literature

1. Krutikov M.G. Pharmacokinetics of antibacterial drugs in burned [Electronic resource] Internet-journal “Combustiology”, 2003, 16-17.URL: www.burn.ru/all/number/show/?id = 3543 (date of access: 05/31/2014).
2. Yakovlev S.V. Systemic antibiotic therapy of burn disease. Basic Research, 2013, 3 (1): 184-188.
URL: www.rae.ru/fs/?section=content&op=show_article&article_id=10000385 (date accessed: 05/28/2014).
3. Bassetti M. Empiric Therapy of Gram-positive Bloodstream Infections and Pneumonia. M. Bassetti, G. Villa. In: J.-L. Vincent (Ed.). Annual Update in Intensive Care and Emergency Medicine.Springer-Verlag 2012: 264-277.
4. Bassetti M. New approaches for empiric therapy in Gram-positive sepsis. M. Bassetti, F. Ginoccio, D.R. Giacobbe. Minerva Anestesiol. 2011, 77: 821-827.
5. Boucher HW. Perspectives on daptomycin resistance, with emphasis on resistance in Staphylococcus aureus. H.W. Boucher, G. Sakoulas. Clin. Infect. Dis. 2007, 45: 601-608.
6. Figueroa DA. Safety of high-dose intravenous daptomycin treatment: three-year cumulative experience in a clinical program.D.A. Figueroa, E. Mangini, M. Amodio-Groton et al. Clin. Infect. Dis. 2009, 49: 177-180.
7. Hidron AI. Antimicrobial-Resistant Pathogens Associated With Healthcare-Associated Infections: Annual Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007. Hidron AI, Jonathan RE, Patel J, Horan TC, Sievert DM, Pollock DA, Fridkin SK. Infect. Control. Hosp. Epidemiol. 2008, 29: 996-1011.
8. Huang SS.Methicillin-Resistant Staphylococcus aureus Infection and Hospitalization in High-Risk Patients in the Year following Detection. Huang SS, Hinrichsen VL, Datta R, Spurchise L, Miroshnik I, Nelson K, Platt R. PLoS ONE, 2011, 6 (9).
9. Jeffers MN. A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia. Jeffres MN, Isakow W, Doherty JA, Micek ST, Kollef MH. Clin.Ther., 2007, 29: 1107-1115.
10. Klevens RM. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. Klevens RM, Morrison MA, Nadle J et al. JAMA 2007,298: 1763-1771.
11. Lagace-Wiens P, Adam H, Nichol K, Decorby M, Mulvey M, Karlowsky J. Vancomycin and Daptomycin MIC Creep in Staphylococcus spp.in Canada – Analysis of 4642 S. aureus and 497 S. epidermidis isolates from 2007–2010 : Interscience Conference on Antimicrobial Agents and Chemotherapy.Chicago, USA, 2011.
12. Luzzaro F. Prevalence and epidemiology of microbial pathogens causing bloodstream infections: results of the OASIS multicenter study. Luzzaro F, Ortisi G, Larosa M, Drago M, Brigante G, Gesu G. Diagn. Microbiol. Infect. Dis. 69: 363-369.
13. Wisplinghoff H. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB.Clin. Inf. Dis. 2004,39: 309-317.

New drugs to fight MRSA infection | News

Treatment of methicillin-resistant Staphylococcus aureus is a major challenge in modern medicine. Among staphylococcal infections worldwide, MRSA is becoming increasingly common and is a cause of considerable concern. According to the US Centers for Disease Control and Prevention, this pathogen causes more than 70 thousand infections and more than 10 thousand deaths every year.

To complicate matters, the list of antibiotics that are effective against MRSA is very narrow. The use of vancomycin and linezolid is often associated with the development of serious side effects. The effect of co-trimoxazole (a combination of sulfamethoxazole and trimethoprim) on methicillin-resistant staphylococcus aureus is unpredictable, therefore it is rarely used in clinical practice. In addition, the resistance of MRSA to different classes of antibiotics is growing steadily.

New drugs developed by researchers at the University of Connecticut have shown promising results.The principle of their work is to disrupt the work of a bacterial enzyme involved in the exchange of folic acid. Trimethoprim also acts on bacteria in a similar way, but over the years of its use, new isoforms of enzymes have appeared, which it has no effect on.

The key difference between the new agents is that the existing and possible variants of the enzyme structure were taken into account in their development. As a result, it was possible to create antibiotics that affect a wide range of isoforms.If the enzyme changes its structure enough to avoid the effects of the new drug, then it will no longer be able to perform its function, and the bacteria will die anyway.

Nine strains of methicillin-resistant staphylococcus were taken for testing, six of which were also resistant to co-trimoxazole. Some strains have shown resistance to other antibiotics, for example, to drugs of the tetracycline series. According to the authors, these strains were obtained in the course of clinical practice.However, despite the high resistance, none of the pathogens were resistant to the new drugs. This successful result has already been published in the journal Cell Chemical Biology.

However, scientists are not satisfied with what has already been achieved: now their goal is to collect MRSA samples from all over the United States. In their opinion, this may allow them to discover new mechanisms of antibiotic resistance. In addition, this will undoubtedly allow demonstrating the effectiveness of new agents in the fight against various strains of methicillin-resistant Staphylococcus aureus.

According to ScienceDaily.

Experimental Endocarditis Model of Methicillin Resistant Staphylococcus aureus (MRSA) in Rat

1. Preparation of MRSA strains of infection

1. Inoculate a loopful culture of MRSA from a tube stock at -80 ° C to lamb blood Trypticase soy agar (TSA) plate (see Table of specific reagents and equipment), and incubate at 37 ° C overnight.
2. Check the purity of the culture on a blood agar plate (as the phenotype of the colony) to ensure there is no contamination.
3. Select one of the sheep’s colony TSA blood plate and inoculate the colonies in 5 ml of Trypticase Soy Broth (TSB) in a 15 ml snap-topped tube.
4. Incubate at 37 ° C overnight with shaking at 200 rpm.

2. Preparing the surgery Catheters

Cut polyethylene tubing (PE10, Becton Dickinson, order no. 427 401) to 10 cm long, and melt one end by pressing the tip with sterile forceps. The purpose of sealing one end of the catheter is to avoid bleeding during catheterization.

3. Pre-preparation of urgery and anesthesia

1. Place Sprague-Dawley rats (Harlan, Indianapolis, Indiana female, 250-300 grams) into a chamber containing isofluorane-oxygen gas mixture (50%: 50%) before anesthesia enters by force (for example, the muscles are relaxed and the pedal reflexes are absent), and also to keep the animals in a state of anesthesia during the operation on the gas mixture.
2. Cleanse the neck area from the chin to just below the sternum with Betadine and 70% ethanol.

4. Surgical procedures

1. Use sterile throughout the operation. Make an incision (1-1.5 cm) vertically just through the skin of the neck above the sternum.
2. Using blunt dissection, divide the faceplate to expose the right carotid artery using 2 pairs of dentate curved forceps.
3. Gently pull up from the artery to the neck cavity, and after two 10 cm lengths of silk suture along the artery and tie from the artery to the exposed head end, place a clip on the arteries to prevent bleeding.
4. Make a small hole in the upper part of the artery with an introducer catheter (Becton Dickinson, no. 406 999), insert the catheter with forceps through the hole in the artery, remove the clip and push the catheter towards the heart until resistance is applied.
5. Tie loosely suture around the tail end of the artery and secure the catheter in place of the suture with silk when the catheter is in the position defined by: a) catheter length (4-5 cm), II), resistance to further development and III), pulsation of the catheter with heartbeat.Leave the catheter in place for the rest of the experiment.
6. Reduce excess suture and catheter ends, and make sure there is no bleeding from the catheter. Tuck the ends under the skin of the neck and close with skin clips.
7. Place rat in a cage in a warm place until it recovers from anesthesia, and provide food and water. Check rats frequently during and after recovery from anesthesia.
8. This operation is a “Category E” procedure. The procedure is performed painlessly with analgesics, as the MRSA infection accompanies the suffering of the animal.

5. MRSA infection

1. Infection can be performed 1 to 7 days after surgery, but keep constant during the experiment.
2. Clean rat tail with 70% ethanol, and inject 0.5 ml of MRSA into the desired cells (10 ⁴ – 10 ⁶ CFU / animal of most strains Staphylococcus aureus). With a 27 G 1/2 in. Tail vein needle Caution: MRSA culture is Biosafety Level 2 (BSL2) and has a moderate potential hazard to personnel and the environment.
3. Keep pressure at the site until hemostasis occurs before the rat returns to the cage.

6. Sacrifice of Rats and Tissue Culture Target

1. Sacrifice of rats f injection of sodium phenobarbital (200 mg / Kg) after 1 to 6 days after infection.
2. Place the rat on its back and wipe the chest with 70% ethanol.
3. Make a V-shaped incision in the chest under the sternum, and cut the cartilage of the ribs on each side of the sternum to reveal the heart.
4. Pull up the heart gently and clip into the heart tissue close to the aorta and dissect until the heart is released.
5. Place the heart in a sterile Petri dish with 4×4 inches in cheesecloth, make an incision through the left ventricle inner wall and open the left-sided chamber.
6. Inspect visually for catheter. Check and remove vegetation from the valve with scissors and forceps.
7. Weigh and homogenize the vegetation, and make serial dilutions of PBS with quantitative culture.

7. Representative Results

Immediately after inserting the catheter into the artery and pushing the catheter 4-5 cm towards the heart, the resistance will be experiencing. If no resistance is felt, the catheter cannot be successfully inserted into the left side of the heart chamber, which may affect the placement of the catheter. The correct placement of the previously published catheter ⁹ is shown in Figure 1 .

Part of the MRSA infection samples must be quantitatively cultured to ensure the exact number of viable bacteria in the infection and the purity of the infection of the sample.In addition, the organism recovered from the vegetation should be the same as those used in sowing.

Table 1 shows an example of the virulence of S. aureus strain in the rat endocarditis model, which was previously published ^9. All animals face a seed problem of 10 ⁵ 10 ⁶ CFU and yields from 3 Up to 6 days after infection, developed endocardits with high S. aureus density in cardiac vegetation, as well as kidney and spleen (

Figure 1. The catheter is in the right place (left side of the heart chamber), and numerous vegetation is visible throughout the aortic valve ^9.

9035 30 ± 0.64

SD, standard deviation. p <0.001 in relation to 10 ⁵ or 10 ⁶ CFU call of animals.

Table 1. S. aureus density in cardiac vegetation with different inoculum in rat model endocarditis ^9.

Subscription Required. Please recommend JoVE to your librarian.

Current problems and solutions for MRSA infections | Zyryanov

1.Lowy F.D. Staphylococcus aureus infections. N Engl J Med 1998; 339 (8): 520-532

2. Romanov A.V., Dekhnich A.V., Sukhorukova M.V., Skleenova E.Yu., Ivanchik N.V. et al. Antibiotic resistance of nosocomial strains of Staphylococcus aureus in hospitals in Russia: results of a multicenter epidemiological study MARATHON in 2013-2014. Wedge microbiol antimicrobial chemother 2017; 19 (1): 57-62

3.Moet G.J., Jones R.N., Biedenbach D.J. et al. Contemporary causes of skin and soft tissue infections in North America, Latin America, and Europe: report from the SENTRY Antimicrobial Surveillance Program (1998-2004). Diagn Microbiol Infect Dis 2007; 57: 7-13.

4. Center for Disease Control and Prevention (CDC). Antibiotic resistance threats in the United States, 2013. Available at ttp: //www.cdc.gov/drugre-sistance/pdf/ar-threats-2013-508.pdf. [Accessed 5 November 2016].

5. European Center for Disease Prevention and Control. Antimicrobial resistance surveillance in Europe. 2014. Available at: ttp: //ecdc.europa.eu/en/publications/publications/antimicrobial-resistance-europe-2014.pdf. Accessed 29 October 2016]

6. The Center for Disease Dynamics, Economics and Policy (CDDEP).The state of the world’s antibiotics 2015. Available at https://cddep.org/sites/default/files/swa_2015_final.pdf. [Accessed 30 October 2016].

7. Dukic V. M., Lauderdale D. S., Wilder J. et al. Epidemics of community-associated methicillin-resistant Staphylococcus aureus in the United States: a meta-analysis. PLoS One 2013, 8.E52722.

8.Li X., Chen Y., Gao W. et al. Epidemiology and outcomes of complicated skin and soft tissue infections among inpatients in Southern China from 2008 to 2013. PLoS One 2016; 11: e0149960.

9. Sader H.S., Mendes R.E., Jones R.N., Flamm R.K. Antimicrobial susceptibility patterns of community- and hospital-acquired methicillin-resistant Staphylococcus aureus from United States Hospitals: results from the AWARE Ceftaroline Surveillance Program (2012-2014).Diagn Microbiol Infect Dis 2016; 86: 76-79.

10. Bassetti M., Righi E., Peghin M. et al. Is first-line antimicrobial therapy still adequate to treat MRSA in the ICU? A report from a highly endemic country. Crit Care 2016; 20: 246.

11. Sakonlas G., Moelering R.C. Increasing antibiotic resistance among methicillin-resistant Staphylococcus aureus strains.Clin Infect Dis. 2008; 46 (Suppl 5): S360-367.

12. Bassetti M., Nicco E., Mikulska M. Why is community-associated MRSA spreading across the world and how will it change clinical practice? Int J Antimicrob Agents 2009; 34 (Suppl 1): S15-S19.

13. Shashindran N., Nagasundaram N., Thappa D.M., Sistla S. Can Panton Valentine Leukocidin gene and clindamycin susceptibility serve as predictors of community origin of MRSA from skin and soft tissue infections? J Clin Diagn Res 2016; 10: DC01-DC04.

14. Callejo-Torre F., Eiros Bouza J. M., Olaechea Astigarraga P. et al. Risk factors for methicillin-resistant Staphylococcus aureus colonization or infection in intensive care units and their reliability for predicting MRSA on ICU admission. Infez Med 2016; 24: 201-209.

15. Dryden M.S. Complicated skin and soft tissue infection.J Antimicrob Chemother 2010; 65: 35-44.

16. Surgical infections of the skin and soft tissues. Russian national recommendations. Ed. B.R. Gelfand. Moscow: 2015

17. Eryukhin I.A., Gel’fand B.R., Shlyapnikov S.A. Surgical infections. SPb .: 2003

18.DiNubile M.J., Lipsky B.A. Complicated infections of skin and skin structure infections: When infection is more than skin deep. J Antimicrob Chemother. 2004; 53: 37-50.

19. Pulgar S., Mehra M., Quintana A. et al. The epidemiology of hospitalized cases of skin and soft tissue infection in Europe. 18th European Congress of Clinical Microbiology and Infectious Diseases. Barcelona, ​​Spain, 2008. Abstr. P821.

20.Kozlov R.S, Krechikova O.I., Ivanchik N.V. et al. Etiology of Nosocomial Bacterial Infections in Russia. Rosnet Study Group. Proceedings of the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2008 Oct 25-28; Washington, DC, USA; p. 572, abst. K-4108.

21. Khachatryan H.H., Chupalov M.O. Postoperative complications: a modern perspective on prevention and treatment. Surgical practice. 2013; 4

22.Surgical infections: a practical guide. Ed. I.A. Eryukhina, B.R. Gelfand, S.A. Shlyapnikov. M .: Litterra, 2006

23. Shlyapnikov S.A. Surgical soft tissue infections are an old problem in a new light. Infections in surgery. 2003; 1 (1): 14-21

24. Zervos M. J., Freeman K., Vo L. et al. Epidemiology and outcomes of complicated skin and soft tissue infections in hospitalized patients.J Clin Microbiol 2012; 50: 238-245

25. Scientific report on the results of the study of antibiotic resistance of bacterial causative agents of nosocomial infections in departments with intensive use of antibiotics in hospitals in Russia (ReVANSH). Research Institute for Antimicrobial Chemotherapy. Smolensk, 2009

26. Stevens D.L., Bisno A.L., Chambers H.F. et al. Practice Guidelines for the Diagnosis and Management of Skin and Soft tissue Infections: 2014 Update by the Infectious Diseases Society of America. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. Schneider-Lindner V. et al. Emery infect Dis 2007; 13: 994-1000.

27. Gel’fand B.P., Belotserkovsky B.Z., Milyukova I.A., Gelfand E.B. Epidemiology and nosological structure of nosocomial infections in the intensive care unit of a multidisciplinary hospital.Infec Surgeon 2014; 4: 24-36

28. Kollef M. et al. Economic impact of ventilator-associated pneumonia in large matched cohort. Infect Control Hosp Epidemiol 2012; 33: 250-256

29. Nosocomial pneumonia in adults. Russian national recommendations. M .: Borges, 2009; 90

30.Pneumonia in adults: diagnosis and management. NICE guidelines [CG191]. Published date: December 2014.

31. Torres A., Ferrer M., Badia J. Treatment Guidelines and outcomes of hospital-acquired and ventilator-associated pneumonia. Clin Infect Dis 2010; 51: 48-53.

32. Cilloniz C. et al. Hospital-acquired pneumonia in ICU. Int J Intensive Care – 2013; 20 (1): 18-23.

33. Chalmers J. et al. Epidemiology, antibiotic therapy, and clinical outcomes in healthcare-associated pneumonia. Clin Infect Dis 2011; 53 (2): 107-113.

34. Rello J. et al. Epidemiology and outcomes of ventilator-associated pneumonia in large US database. Chest 2002; 122: 2115-2121.

35.Jones R.N. Clin Infect Dis 2010; 51 (1): 81-87.

36. Koulenti D. et al. CCM 2009; 37: 23-60.

37. Chuchalin A.G., Sinopal’nikov A.I., Kozlov P.C. et al. Clinical guidelines for the diagnosis, treatment and prevention of severe community-acquired pneumonia in adults. M .: Publishing house “M-Vesti” 2014; 92.

38.Macfarlane J. Semin Respir Infect 1994; 9: 153-165.

39. Welte T. et al. Thorax 2012; 67: 71-79.

40. Udeani C. et al. Hosp Prac 2014; 42: 109-115.

41. Torres A. et al. Eur Respir J 2015; 45: 1353-1363.

42.O’Grady N. P., Aleksander M., Burns L. A. et al. Healthcare Infection Control Practices Advisory Committee. Guidelines for the prevention of intravascular catheter-related infections. Am J Infect Control 2011; 39: 4 (Suppl 1): 1-34.

43. Abad C. L., Nasia Safdar. Clin Rev 2012.

44. Jean-Louis V. et al. JAMA. 2009; 302 (21): 2323-2329.

45. Hollenbeak S. The cost of catheter – related bloodstream infections. J. Infusion Nursing 2011; 34 (1): 1-110.

46 European Center for Disease Prevention and Control (ECDC) 2009; 201.

47. Ruhe J. J., Smith N., Bradsher R. W., Menon A. Community-onset methicillinresistant Staphylococcus aureus skin and soft-tissue infections: impact of antimicrobial therapy on outcome.Clin Infect Dis 2007; 44: 777-784.

48. Eagye K. J., Kim A., Laohavaleeson S. et al. Surgical site infections: does inadequate antibiotic therapy affect patient outcomes? Surg Infect (Larchmt) 2009; 10: 323-331.

49. John J., Engemann J.J. et al. Adverse clinical and economic outcomes attributable to methicillin resistance among patients with Staphylococcus aureus surgical site infection.Clin Infect Dis. 2003; 36: 592-598.

50. Dekhnich A.V., Danilov A.I. Daptomycin: a review of pharmacological, clinical and microbiological parameters. Wedge microbiol antimicrobial chemother 2010; 12 (4)

51. A. V. Nikitin. Ceftaroline fosamil is a broad-spectrum cephalosporin antibiotic for the treatment of community-acquired pneumonia and complicated infections of the skin and subcutaneous tissue.Antibiotics and Chemother 2011; 56: 7-8

52. White B., Seaton R.A. Complicated skin and soft tissue infections: literature review of evidence for experience with daptomycin. Infect Drug Resist 2011; 4: 115-127.

53. Locke J.B. et al. Novel Ribosomal Mutations in Staphylococcus aureus strains identified through Selection with the Oxazolidinones linezolid and Torezolid.Antimicrob Agents Chemother 2009; 53 (12): 5265-5274.

54. Morales G., Picazo J. J., Baos E. et al. Resistance to linezolid is mediated by the CRF gene in the first report of an outbreak of linezolid-resistant Staphylococcus aureus. Clin Infect Dis 2010; 50 (6): 821-825.

55. Sukhorukova M.V., Skleenova E.Yu., Ivanchik N.V. et al.Antibiotic resistance of nosocomial strains of Staphylococcus aureus in hospitals in Russia: results of a multicenter epidemiological study MARATHON in 2011-2012. Wedge microbiol antimicrobial chemother 2014; 16 (4): 280-286.

56. Stevens D. L., Bisno A. L., Chambers H. F., et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis 2005; 41: 1373-1406.

57. Stevens D.L., Bisno A.L., Chambers H.F. et al. Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis 2014; 59: e10-e52; Erratum in: Clin Infect Dis 2015; 60: 1448.

58. Itani K.M., Dryden M. S., Bhattachatyya et al. Efficacy and safety of linezolid versus vancomycin for the treatment of complicated skin and soft tissue infections proven to be caused by methicillin-resistant Staphylococcus aureus. Am J Surg. 2010; 199 (6): 804-816.

59. Patrick M.F, McKay C.M. et al. Increased incidence of skin and soft tissue infections and associated antimicrobial use: a population-based study. Antimicrob Agents Chemother 2012; 56: 6243-6249.

60. May A.K, Stafford R.E., Bulger F.M. et al. Surgical Infection Society. Treatment of complicated skin and soft tissue infections. Surg Infect 2009; 10: 467-499.

61. Ye ZK., Li C., Zhai S.D. Guidelines for therapeutic drug monitoring of vancomycin: a systematic review. PLoS One 2014; 9: e99044.

62.Brink A.J. Does resistance in severe infections caused by methicillin-resistant Staphylococcus aureus give you the ‘creeps’? Curr Opin Crit Care 2012; 18: 451-459.

63. Gonzalez-Ruiz A., Seaton R.A., Hamed K. Daptomycin: an evidence-based review of its role in the treatment of Gram-positive infections. Infect Drug Resist 2016; 9: 47-58.

64.Eliopoulos G. M., Thauvin C., Gerson B. et al. In vitro activity and mechanism of action of A21978C1, a novel cyclic lipopeptide antibiotic. Antimicrob Agents Chemother 1985; 27: 357-362.

65. Hanberger H., Nilsson L.E., Maller R., Isaksson B. Pharmacodynamics of daptomycin and vancomycin on Enterococcus faecalis and Staphylococcus aureus demonstrated by studies of initial killing and postantibiotic effect and influence of Ca2 + and albumin on these drugs.Antimicrob Agents Chemother 1991; 35: 1710-1716.

66. Schriever C.A., Fernandez C., Rodvold K.A., Danziger L.H. Daptomycin: a novel cyclic lipopeptide antimicrobial. Am J Health-Syst Pharm 2005; 62: 1145-1158.

67. Dekhnich A.V., Danilov A.I. Daptomycin: a review of pharmacological, clinical and microbiological parameters. Wedge microbiol antimicrobial chemother 2010; 12 (4).

68. White B., Seaton R.A. Complicated skin and soft tissue infections: literature review of evidence for experience with daptomycin. Infection and Drug Resistance. 2011; 4: 115-127.

69. Arbeit R.D., Maki D., Tally F.P., Campanaro E., Eisenstein B.I. The safety and efficacy of daptomycin for the treatment of complicated skin and skin-structure infections.Clin Infect Dis 2004; 38: 1673-1681.

70. Nathwani D. Developments in outpatient parenteral antimicrobial therapy for Gram-positive infections in Europe, and the potential impact of daptomycin. J Antimicrob Chemotherapy. 2009; 64: 447-453.

71. Traunmuller F., Schintler M. V., Metzler J. et al. Soft tissue and bone penetration ability of daptomycin in diabetic patients with bacterial foot infections.J Antimicrob Chemother. 2010; 65 (6): 1252-1257.

72. Karlowsky J.A., Biedenbach D.J., Bouchillon S.K. et al. In vitro activity of Ceftaroline against bacterial pathogens isolated from patients with skin and soft tissue and respiratory tract infections in African and Middle Eastern countries: AWARE global surveillance program 2012-2014. Diagn Microbiol Infect Dis 2016; 86: 194-199.

73.Matzneller P., Lackner E., Lagler H. et al. Single- and repeated-dose pharmacokinetics of ceftaroline in plasma and soft tissues of healthy volunteers for two different dosing regimens of ceftaroline fosamil. Antimicrob Agents Chemother 2016; 60: 3617-3625.

74. Kozlov R.S., Golub A.V. Ceftaroline – sui generis. Wedge microbiol antimicrobial chemother 2013; 15 (2): 124-130

75.Lipsky B. A., Cannon C. M., Ramani A. et al. Ceftaroline fosamil for treatment of diabetic foot infections: the CAPTURE study experience. Diabetes Metab Res Rev 2015; 31: 395-401.

76. Andreeva I.V., Stetsyuk O.U., Kozlov R.S. Tigecycline: prospects for clinical use. Wedge microbiol antimicrobial chemother 2010; 12 (2): 127-145.

77.Guirao X., Sanchez Garcia M., Bassetti M. et al. Safety and tolerability of tigecycline for the treatment of complicated skin and soft-tissue and intraabdominal infections: an analysis based on five European observational studies. J Antimicrob Chemother 2013; 68 (Suppl 2): ​​ii37-ii44.

78. Bergeron J., Ammirati M., Danley D. et al. Glycylcyclines bind to the high-affinity tetracycline ribosomal binding site and evade tet (M) – and tet (O) -mediated ribo-somal protection.Antimicrob Agents Chemother 1996; 40 (9): 2226-2228.

79. Tigacil. Official Pfizer product information. http://www.pfizer.ru/activity/?id=30&n=485.

80. Ellis-Grosse E. J., Babinchak T., Dartois N. et al; Tige-cycline 300 cSSSI Study Group; Tigecycline 305 cSSSI Study Group. The efficacy and safety of tigecycline in the treatment of skin and skin-structure infections: results of

81.double-blind phase 3 comparison studies with vancomycin-aztreonam. Clin Infect Dis 2005; 41 (Suppl 5): S341-353.

82. Leadbetter M. R., Adams S. M., Bazzini B. et al. Hydrophobic vancomycin derivatives with improved ADME properties: discovery oftelavancin (TD-6424). J Antibiot (Tokyo). 2004 May; 57 (5): 326-336.

83. Higgins D.L., Chang R., Debabov D. V., et al. Telavancin, a multifunctional lipoglycopeptide, disrupts both cell wall synthesis and cell membrane integrity in methicillinresistant Staphylococcus aureus. Antimicrob Agents Chemother 2005; 29: 1127-1134.

84. Dekhnich A.V., Kozlov R.S., Zubareva N.A., Popov D.A., Romanov A.V., Rudnov V.A. Telavancin is a new drug that is active against multidrug-resistant gram-positive pathogens.Clinical and microbiological aspects in questions and answers review of pharmacological, clinical and microbiological parameters. Wedge microbiol antimicrobial chemother 2015; 17 (2): 127-145

85. Draghi D.C., Jones M.E., Flamm R.K., Thornsberry C., Sahm D.F. Telavancin activity against current and diverse populations of enterococci and Streptococcus pneumoniae. Presented at the 45th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, December 16-19, 2005, Washington, DC.

86. Madrigal A.G., Basuino L., Chambers H.F. Efficacy of telavancin in a rabbit model of aortic valve endocarditis due to methicillin-resistant Staphylococcus aureusor vancomycin-intermediate Staphylococcus aureus. Antimicrob Agents Chemother 2005; 49: 3163-3165.

87. Corey G.R., Kollef M.H., Shorr A.F. et al. Telavancin for hospital-acquired pneumonia: clinical response and 28-day survival.Antimicrob Agents Chemother 2014; 58: 2030-2037.

88. Dunbar L.M., Tang D.M., Manausa R.M. A review of telavancin in the treatment of complicated skin and skin structure infections (cSSSI). Therapeutics and Clinical Risk Management 2008: 4 (1) 235-244.

89. Tubau F., Fernández-Roblas R., Linares J., Martn R., Soriano F. In vitro activity of linezolid and 11 other antimicrobials against 566 clinical isolates and comparison between NCCLS microdilution and Etest methods J Antimicrob Chemotherapy 2001 May; 47 (5): 675-680.

90. Bassetti M, Baguneid M, Bouza E, et al. European perspective and update on the management of complicated skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus after more than 10 years of experience with linezolid. Clin Microbiol Infect 2014; 20 (Suppl 4): 3-18.

91. Yue J., Dong B. R., Yang M. et al.Linezolid versus vancomycin for skin and soft tissue infections. Cochrane Database Syst Rev 2016; 1: CD008056.

92. Sharpe J.N., Shively E.H., Polk H.C. Jr. Clinical and economic outcomes of oral linezolid versus intravenous vancomycin in the treatment of MRSA-complicated, lower-extremity skin and soft-tissue infections caused by methicillinresistant Staphylococcus aureus. Am J Surg 2005; 189: 425-428.

93.Rubinstein E., Isturiz R., Standiford H. C. et al. Worldwide assessment of linezolid’s clinical safety and tolerability: comparator-controlled phase III studies. Antimicrob Agents Chemother 2003; 47: 1824-1831.

94. Cattaneo D., Orlando G., Cozzi V. et al. Linezolid plasma concentrations and occurrence of drug-related haematological toxicity in patients with grampositive infections. Int J Antimicrob Agents 2013; 41: 586-589.

95. Go A.C., Golightly L.K., Barber G.R., Barron M.A. Linezolid interaction with serotonin reuptake inhibitors: report of two cases and incidence assessment. Drug Metabol Drug Interact 2010; 25: 41-47.

96. Wilson D.N., Schluenzen F., Harms J.M., Starosta A.L., Connell S.R., Fucini P. The oxazolidinone antibiotics perturb the ribosomal peptidyl-transferase center and effect tRNA positioning.Proc Natl Acad Sci. 2008; 105 (36): 13339-13344.

97. Jones R.N. et al. TR-700 in vitro activity against and resistance mutation frequencies among Gram-positive pathogens. Antimicrob Chemotherapy 2009; 63: 716-720.

98. Schaadt R., Sweeney D., Shinabarger D., Zurenko G. ip vitro activity of TR-700, the active ingredient of the antibacterial prodrug TR-701, a novel oxazolidinone antibacterial agent.Antimicrob Agents Chemother 2009; 53 (8): 3236-3239.

99. Sahm D.F. et al. Results of the surveillance of Tedizolid activity and resistance program: in vitro susceptibility of gram-positive pathogens collected in 2011 and 2012 from the United States and Europe. Diagn Microbiol Infect Dis. 2015 Feb; 81 (2): 112-118.

100. Kisgen J.J., Mansour H., Unger N.R., Childs L.M. Tedizolid: a new oxazolidinone antimicrobial. Am. J. Health Syst. Pharm. 2014; 71 (8): 621-633.

101. Im W.B., Choi S.H., Park J.Y. et al. Discovery of torezolid as a novel 5-hydroxymethyl-oxazolidinone antibacterial agent. Eur J Med Chem 2011; 46 (4): 1027-1039.

102. Brown S.D., Traczewski M.M. Comparative in vitro antimicrobial activities of torezolid (TR-700), the active moiety of a new oxazolidinone, torezolid phosphate (TR-701), determination of tentative disk diffusion interpretive criteria, and quality control ranges. Antimicrob Agents Chemother 2010; 54 (5): 2063-2069.

103. Choi S., Im W., Bartizal K. Activity of tedizolid phosphate (TR-701) in murine models of infection with penicillin-resistant and penicillin-sensitive Streptococcus pneumoniae.Antimicrob Agents Chemother. 2012; 56 (9): 4713-4717.

104. Prokocimer P., Bien P., Surber J. et al. Phase 2, randomized, double-blind, dose-ranging study evaluating the safety, tolerability, population pharmacokinetics, and efficacy of oral torezolid phosphate in patients with complicated skin and skin structure infections. Antimicrob Agents Chemother 2011; 55 (2): 583-592.

105.Moran G.J., Fang E., Corey G.R. et al. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTAB-LISH-2): a randomized, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis 2014 Jun 5. [Epub ahead of print].

106. Colca J.R., McDonald W.G., Waldon D.J. et al. Cross-linking in the living cell locates the site of action of oxazolidinone antibiotics.J Biol Chem 2003; 278 (24): 21972-21979.

107. Flanagan S., Fang E., Munoz K.A., Minassian S.L., Prokocimer P.G. Single-and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid. Pharmacotherapy 2014; 34 (9): 891-900.

108. Bien P., Muonz K. A., Bohn J. et al. Human pharmacokinetics of TR-700 after ascending single oral doses of the prodrug TR-701, a novel oxazolidi-none antibiotic.Poster presented at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy, October 25-28, 2008, Washington DC.

109. Flanagan S.D., Bien P.A., Munoz K.A., Minassian S.L., Prokocimer P.G. Pharmacokinetics of tedizolid following oral administration: single and multiple dose, effect of food, and comparison of two solid forms of the prodrug. Pharmacotherapy 2014; 34 (3): 240-250.

110.Flanagan S., Passarell J., Lu Q., Fiedler-Kelly J., Ludwig E., Prokocimer P. Tedizolid population pharmacokinetics, exposure response, and target attainment. Antimicrob Agents Chemother 2014; 58 (11): 6462-6470.

111. Housman S. T., Pope J. S., Russomanno J. et al. Pulmonary disposition of tedizolid following administration of once-daily oral 200-milligram tedizolid phosphate in healthy adult volunteers. Antimicrob Agents Chemother 2012; 56 (5): 2627-2634.

112. Flanagan S., Minassian S. L., Morris D. et al. Pharmacokinetics of tedizolid in subjects with renal or hepatic impairment. Antimicrob Agents Chemother 2014; 58 (11): 6471-6476.

113. Shorr A. F., Lodise T. P., Corey G. R. et al. Analysis of the Phase 3 ESTABLISH Trials of Tedizolid versus Linezolid in Acute Bacterial Skin and Skin Structure Infections Antimicrob Agents Chemother 2015; 59 (2): 864-871.

114. Flanagan S., Bartizal K, Minassian S.L. et al. In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions. Antimicrob Agents Chemother 2013; 57 (7): 3060-3066.

115. Belkova Yu.A., Rachina S.A., Kozlov R.S., Golub A.V., Portnyagina U.S., Shamaeva S.Kh.Prospects for the inclusion of tedizolid in the formulary of a Russian multidisciplinary hospital for the treatment of complicated infections of the skin and soft tissues. Wedge microbiol antimicrobial chemother 2016; 18 (3): 174-185

Phage therapy for MRSA-infection of joint prosthesis

The journal Antibiotics describes * a clinical case of successful bacteriophage treatment of a chronic joint prosthesis infection caused by methicillin-resistant staphylococcus (MRSA)

A patient, a 72-year-old male with obesity (BMI 41) and hyperlipidemia, was hospitalized with chronic MRSA infection of a knee joint prosthesis.Twenty years earlier, he had suffered septic arthritis and an intraosseous abscess of the right knee caused by methicillin-sensitive staphylococcus, which was treated with IV cefazolin. A year later, the patient suffered a fracture of the distal femur, which required fixation with a lateral plate. He later developed severe osteoarthritis and in 2012 underwent arthroplasty of the right knee joint. In 2014, the patient developed an infection of the joint prosthesis caused by Staphlylococcus epidermidis , underwent open debridement (DAIR), and after recurrence of the infection, a two-stage revision.In 2016, an injury to the right knee resulted in erythema and effusion, and arthrocentesis showed the presence of MRSA. DAIR was performed, and three weeks later, due to worsening symptoms, another one. Therapy with vancomycin IV and intra-articular (IV) was started. After 5 weeks, vancomycin was replaced with IV daptomycin, and IV vancomycin was extended for three weeks. The patient was then transferred to oral doxycycline therapy, which lasted 2 years and successfully suppressed MRSA. Three weeks after completing the doxycycline course, a relapse occurred and MRSA was re-detected on arthrocentesis.Against the background of doxycycline, which was again prescribed, the symptoms worsened. Through the above-mentioned fracture of the distal femur, which did not heal to the end, a two-stage revision of the joint was impossible, the patient refused amputation. The patient was offered DAIR using IV and IV bacteriophages.

MRSA strains isolated from the joint were sent to a commercial laboratory for the selection of specific phages with high lytic activity. During DAIR, numerous fistulas, significant soft tissue damage, extensive suppuration, erosion of the distal femur and significant damage to the prosthesis, which could no longer be repaired, were identified.When DAIR was certified, the patient received i / c bacteriophages (5.4×10 ⁹ PFU in 10 ml of saline). At the same time, a course of daptomycin intravenously was started 1000 mg daily, and the next day – a course of bacteriophages intravenously daily (2.7 × 10 ⁹ PFU in 50 ml of saline).

See also: Bacteriophages in the treatment of infective endocarditis artificial valve

After the third dose of IV bacteriophages, the patient showed a sharp increase in the level of hepatic transaminases AST and ALT: 136 and 86 times, respectively.The next day, the level of transaminases increased further, and the treatment with bacteriophages was discontinued. Indicators of bilirubin, alkaline phosphatase, creatine kinase, prothrombin time were normal. Infectious liver lesions were excluded. Ultrasound showed hepatomegaly, but no other organ abnormalities were found. The course of daptomycin was extended to 6 weeks. AST and ALT readings returned to normal 10 days after lifting.

Three weeks after stopping antibiotic therapy, the patient underwent debridement.No manifestations of an active infectious process were observed; microbiological analyzes of various tissues showed the absence of infection. A static spacer with vancomycin was installed and an intravenous injection of bacteriophages was performed (2.7 × 10 ⁹ PFU in 10 ml of saline). Monitoring of AST and ALT for 5 days showed no increase.

After 2 months, after BMI normalization, the patient was placed with a megaprosthesis. In this case, the patient received i / c bacteriophages (2.7 × 10 ⁹ PFU in 10 ml of saline).The results of bacterial culture from the surgical field were negative. A week later, the patient was discharged from the hospital and sent for rehabilitation.

Infection of an articular prosthesis (infectious arthritis of the artificial joint) is one of the most common complications after arthroplasty (occurs in 1-2% of artificial prostheses), with high mortality rates (more than 20% within 5 years). Joint prosthesis infection is difficult to treat due to bacterial biofilm formation on the surface of the prosthesis.To effectively kill bacteria in biofilms, antibiotic concentrations are required 1000 times higher than those used to kill individual (planktonic) bacteria. Therefore, it is very important to search for new methods of treating joint prosthesis infections, as well as other infections associated with the formation of biofilms.

A promising method for the treatment of antibiotic-resistant infections, in particular those associated with biofilms, is bacteriophages – bacteria viruses that specifically destroy certain types (strains) of bacteria, including those in biofilms, without affecting the normal microflora of the body.